Endocytosis and Physiology: Insights from Disabled-2 Deficient Mice

In the paper

“Tumors/multiple types | Uterine hyperproliferation, Ovarian epithelial growth, Increased tumor incidence”

What the sources say

• ?Not checked — no full text of the sourcecites Yang et al., 2006 source
• Disputed

  The Discussion (page unavailable) says ovarian surface epithelia in Dab2-deficient mice are monolayered and intact, contrary to the claimed epithelial growth. The Results report more preneoplastic lesions in the ovaries of aged mice with a dab2-deleted genotype, but do not describe ovarian epithelial growth. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“The functions of Dab2 in macrophages were suggested to promote inflammation in brain (Jokubaitis et al., 2013), adipose tissue (Adamson et al., 2016), rat spinal cord injury (Ahn et al., 2011, 2015), and central nervous system (Moon et al., 2005).”

What the sources say

• Partly supported

  The Discussion reports that Dab2-dependent macrophage/microglial responses worsen inflammatory tissue damage in experimental autoimmune encephalomyelitis (EAE). But the study locates its EAE findings in the spinal cord, not specifically the brain; the Background mentions brain injury only when describing another study's finding of Dab2 up-regulation, not a demonstrated pro-inflammatory function there. (LLM, conf=0.86)

  cites Jokubaitis et al., 2013 sourceExperimental — accuracy not yet measured
• Disputed

  For the adipose-tissue clause attributed to Adamson et al., the Introduction reports that deleting Dab2 exacerbated adipose tissue inflammation in high-fat-fed mice. The Methods passage likewise says deletion of Dab2 in myeloid cells worsened that inflammation. The source therefore describes DAB2 as restraining, not promoting, inflammation in this setting. (LLM, conf=0.94)

  Checked by a reasoning model — may be wrong.

  cites Adamson et al., 2016 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ahn et al., 2011, 2015

In the paper

“The lack of more noticeable differences in the mammary glands of Dab2 null mice may be due to the compensation of other endocytic adaptors, such as Numb and Arh.”

What the sources say

• Supported

  The Discussion explicitly proposes that compensation by the endocytic adaptors Numb and ARH may explain why Dab2-knockout mammary glands show only subtle differences. It also reports increased Numb and ARH protein levels in Dab2-null mammary epithelial cells (Figure 9). (LLM, conf=0.95)

  cites Tao et al., 2014 source

In the paper

“The increased TGF-beta-stimulated Ras/MAPK activation and subsequent induction of higher expression of survival genes (Boucher et al., 2000; Balmanno and Cook, 2009) may explain the prolonged survival of mammary epithelial cells of Dab2-null mice during involution (Tao et al., 2014).”

What the sources say

• ?Not checked — no full text of the sourcecites Boucher et al., 2000 source
• ?Not checked — no full text of the sourcecites Balmanno and Cook, 2009 source
• Supported

  The Discussion proposes that unsuppressed TGF-beta-induced Ras/MAPK activation may explain the prolonged survival of Dab2-null mammary epithelial cells during involution. Its Figure 8 description links that pathway to expression of cell-survival genes, while the Results report increased Bcl-2 in Dab2-null glands. (LLM, conf=0.94)

  cites Tao et al., 2014 source

In the paper

“Immune system/Treg | No obvious phenotype in vivo; failed to suppress T cells”

• Also stated in: § Roles of Dab2 in immune cells · plain

  “However, mice with Dab2 deletion in Treg cells are healthy in appearance and do not show phenotypes related to autoimmunity defects even at 1 year of age”

What the sources say

• Partly supported

  In Results and Discussion, Dab2 conditional-knockout mice appeared healthy, lacked overt autoimmunity, and had phenotypically similar Treg cells under unperturbed conditions. But the same section reports an in vivo defect: their Treg cells failed to moderate established colitis. Thus, 'no obvious phenotype in vivo' is supported only for the unperturbed mice, not as a general statement about Treg function in vivo. (LLM, conf=0.88)

  cites Jain et al., 2009 sourceExperimental — accuracy not yet measured

In the paper

“Liver/sinusoidal endothelial cells | Increased serum cholesterol”

• Also stated in: § Function in LDL uptake and cholesterol homeostasis · plain

  “Deletion of Dab2 gene in mice only results in a small increase of serum cholesterol level (Moore et al., 2013)”

What the sources say

• Supported

  The Results section (‘Role of Dab2 in cholesterol metabolism in vivo’) reports a small but statistically significant increase in serum total cholesterol in Dab2-deficient mice compared with littermate controls. The Discussion also describes increased serum cholesterol in the mutant mice. (LLM, conf=0.94)

  cites Moore et al., 2013 source
• Partly supported

  The Results report increased serum cholesterol in mice lacking both Dab2 and Arh, not in Dab2-null mice alone. The Discussion says Dab2 ablation alone has a relatively minor impact on serum cholesterol and reports increased liver cholesterol in those mice; liver cholesterol is not serum cholesterol. No page numbers are available in our copy. (LLM, conf=0.83)

  cites Tao et al., 2016a sourceExperimental — accuracy not yet measured

In the paper

“Tumors/multiple types | Uterine hyperproliferation, Ovarian epithelial growth, Increased tumor incidence”

What the sources say

• ?Not checked — no full text of the sourcecites Yang et al., 2006 source
• Partly supported

  The Results section (“Characterization of dab2 conditional mutant mice”; page unavailable) reports an increased incidence of preneoplastic lesions in aged mice with a dab2-deleted genotype. It does not report increased tumor incidence: the authors say studies of tumor phenotypes will be reported elsewhere. The claim also omits that these were conditional mutants rather than constitutive Dab2-null mice. (LLM, conf=0.88)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“though impact of Dab2 deletion on cardiac development is not notable (Morris et al., 2002b; Moore et al., 2013).”

What the sources say

• Partly supported

  The rescue section (page unavailable) reports that mice with Dab2 deleted from the embryo proper appeared normal, were born and survived, supporting no obvious developmental defect under that condition. It does not assess cardiac development specifically; complete Dab2 deletion instead caused early embryonic lethality, as reported in the targeting section (page unavailable). (LLM, conf=0.82)

  cites Morris et al., 2002b sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section on conditional mutant mice reports no detectable developmental defects, and the Conclusion says Dab2 is dispensable for organ development when deletion is restricted to the embryo proper. These findings support a limited developmental impact, but the paper does not specifically assess cardiac development; constitutive deletion instead caused early embryonic lethality. (LLM, conf=0.83)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“By competing with Sos1 for binding to Grb2, Dab2 acts as a negative regulator for Ras/MAPK pathway (Xu et al., 1998; Zhou and Hsieh, 2001).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 1998
• Supported

  The Results state that DOC-2/DAB2 and SOS compete for the same binding site on Grb2. The Discussion says this interaction inhibits the MAP kinase pathway by preventing Grb2 from recruiting SOS. Our copy calls the competing protein “SOS” rather than “Sos1.” (LLM, conf=0.93)

  cites Zhou and Hsieh, 2001 source

In the paper

“Indeed, a role of Dab2 in suppressing Ras/MAPK activation accounts for embryonic development (Yang et al., 2009) and several physiological phenotypes observed in Dab2 null mice (Tao et al., 2014, 2016b).”

What the sources say

• Partly supported

  The Results and Discussion (page not provided) link Dab2-mediated suppression of c-Fos to extraembryonic endoderm organization and show that eliminating c-fos partially rescues early embryonic lethality. They do not establish that Dab2 suppresses Ras/MAPK activation; the Discussion instead describes regulation of activated MAPK’s nuclear entry as an untested hypothesis and identifies an additional c-Fos-independent requirement in development. The separate claim about physiological phenotypes is cited to Tao et al., not this paper. (LLM, conf=0.88)

  cites Yang et al., 2009 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Tao et al., 2014, 2016b

In the paper

“In the absence of Arh, Dab2 in liver endothelial cells regulates the expression of HMG-CoA reductase and cholesterol synthesis in hepatocytes (Tao et al., 2016a).”

What the sources say

• Supported

  The Discussion states that, in the absence of Arh, Dab2-supported LDL uptake in liver sinusoidal endothelial cells can suppress hepatic HMGCR. It also proposes that the resulting cholesterol regulates synthesis in hepatocytes, matching the claim. (LLM, conf=0.92)

  cites Tao et al., 2016a source

In the paper

“Thus, several mechanisms have been suggested for the involvement of Dab2 in TGF-beta pathway, such as receptor recycling, adapting function for Smad activation, or non-canonical TGF-beta signaling through the Ras-MAPK pathway, although the actual operation of these mechanisms in intact animals and physiological settings have yet to be demonstrated.”

What the sources say

• Partly supported

  The Abstract (page unavailable) describes Dab2 as an adaptor linking TGFβ receptors to Smad activation and reports a Dab2–TAK1–JNK signaling mechanism tested in cultured cells. That supports the claim that mechanisms have been proposed without demonstration in intact animals, but the paper does not establish TGFβ receptor recycling or a specifically Ras-mediated MAPK mechanism. (LLM, conf=0.84)

  cites Hocevar et al., 2005 sourceExperimental — accuracy not yet measured
• Partly supported

  The introductory passage describes Dab2 as an adaptor linking TGF-β receptors to Smads, and the Discussion considers a possible Smad-independent MAPK pathway. The Discussion also says that pathway remains under investigation, while the reported TGF-β experiments use cultured cells. Our copy does not specifically propose TGF-β receptor recycling or a Ras–MAPK mechanism, or explicitly state that all the listed mechanisms await demonstration in intact animals. (LLM, conf=0.84)

  cites Prunier and Howe, 2005 sourceExperimental — accuracy not yet measured
• Partly supported

  The paper’s Abstract describes Dab2 as a mediator of TGF-β-induced EMT and says its precise function downstream of hnRNP E1 is difficult to define. It does not identify receptor recycling, Smad activation, or Ras–MAPK signaling as proposed Dab2 mechanisms, nor does it specifically say that those mechanisms remain untested in intact animals or physiological settings. No page number is available in our copy. (LLM, conf=0.79)

  cites Chaudhury et al., 2010 sourceExperimental — accuracy not yet measured

In the paper

“However, in the absence of Arh, the additional loss of Dab2 greatly augments serum LDL and cholesterol levels to an extent similar to that observed in LDL receptor null mice (Tao et al., 2016a).”

What the sources say

• Supported

  The Results report that Arh/Dab2 double-knockout mice had serum cholesterol levels similar to LDLR-knockout mice, with increased cholesterol in LDL as well as HDL and VLDL. The comparison was made in mice on a high-sucrose diet; the paper does not separately state that LDL alone reached the LDLR-knockout level. (LLM, conf=0.91)

  cites Tao et al., 2016a source

In the paper

“Through its PTB domain, Dab2 mediates the attachment of cargos containing transmembrane proteins with an NPXY motif, such as the LDL receptor, EGF receptor, megalin, and integrins, to clathrin coats”

What the sources say

• Partly supported

  The paper’s Abstract and “Dab2 and cargo recognition” section support a model in which Dab2’s PTB domain recognizes LDL-receptor-family FXNPXY motifs and Dab2 links selected cargo to clathrin-coat machinery; the latter section also reports Dab2 association with megalin. The copy does not establish EGF receptors or integrins as Dab2 PTB-domain cargo, so the full list of examples is not supported. No page numbers were available in the indexed passages. (LLM, conf=0.89)

  cites Mishra et al., 2002 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Morris et al., 2002a source
• ?Not checked — no full text of the sourcecites Bonifacino and Traub, 2003 source

In the paper

“Therefore, it was concluded that Dab2 modulates the non-canonical pathways of TGF-beta by suppressing Ras/MAPK activation”

What the sources say

• ?Not checked — no full text of the sourcecites Mulder, 2000 source
• ?Not checked — no full text of the sourcecites Moustakas and Heldin, 2005 source
• ?Could not verify

  The Introduction and the section ‘Direct induction of MAP kinase by TGF-b is mediated by ShcA’ describe TGF-β-induced Ras/MAPK signaling and its attenuation by ShcA mutants. The passages provided and searches for Dab2 and Disabled-2 yielded no discussion of whether Dab2 suppresses that pathway, which is the claim attributed to this source. (LLM, conf=0.73)

  cites Lee et al., 2007 sourceExperimental — accuracy not yet measured

In the paper

“The finding leads to the conclusion that Dab2 does not cooperate but complements Arh in LDL receptor endocytosis in the clearance of serum LDL particles.”

What the sources say

• Partly supported

  The Results report that either Dab2 or Arh can support LDLR-mediated LDL uptake in mouse cells and that having both is not additive in the same cell. The Discussion describes Dab2 as supplementary to Arh in intact mice, supporting the idea that their roles complement one another in circulating LDL clearance. But the paper does not establish the broader claim that they do not cooperate in that clearance; it calls their roles concerted. (LLM, conf=0.83)

  cites Tao et al., 2016a sourceExperimental — accuracy not yet measured

In the paper

“In studies using cultured cells, Dab2 was found to play a role in the endocytosis of LDL receptor, in coordination with Arh”

What the sources say

• Partly supported

  The Abstract and the section ‘Dab2 colocalizes with LDLRs in clathrin-coated pits’ (p. 115) report that Dab2 colocalizes with LDL receptors in cultured cells and suggest a role in their endocytosis. The paper proposes this role rather than directly establishing it, and the passages do not support the claimed coordination with Arh. (LLM, conf=0.88)

  cites Morris and Cooper, 2001 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Maurer and Cooper, 2006 source

In the paper

“Blastocysts/primitive and extraembryonic endoderm early embryos | Failed cell sorting”

What the sources say

• Partly supported

  In “Targeting of the Dab2 locus” (page unavailable), the paper reports disorganized cells in early Dab2-null embryos and reduced or absent inner cell masses in cultured null blastocysts. It does not identify failed cell sorting in primitive or extraembryonic endoderm as the defect; it describes recognizable endoderm layers in the embryos. (LLM, conf=0.82)

  cites Morris et al., 2002b sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Yang et al., 2002b, 2007
• Supported

  In Results, under “Characterization of Dab2 constitutive null mutant embryos” (page not provided), primitive endoderm cells in E4.5 Dab2-null embryos were misplaced within the inner cell mass rather than forming a surface layer. At E5.5, endoderm cells were likewise misplaced and intermixed within the egg cylinder core. These findings support the description of failed cell sorting in early embryos. (LLM, conf=0.91)

  cites Moore et al., 2013 source

In the paper

“In cultured cells, Dab2 modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 1998
• Partly supported

  The “Ras Signalling on endosomes” section (page unavailable) describes endosomal Ras/MAPK signaling and reports Grb2 and mSOS on endosomes. The copy does not mention Dab2 or say that it regulates disassembly of Grb2/Sos1 complexes on clathrin-coated vesicles; searches for Dab2 and the proposed mechanism found no such passage. (LLM, conf=0.83)

  cites Fehrenbacher et al., 2009 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Smith et al., submitted

In the paper

“Indeed, Numb and Arh protein levels are elevated in Dab2-deficient mammary epithelial cells (Tao et al., 2014).”

What the sources say

• Supported

  The Discussion explicitly reports increased Numb and ARH protein levels in Dab2-knockout mammary gland epithelial cells. Its Figure 9 caption describes Western blots of primary mammary epithelial cells and quantifies increases of 2.1-fold for Numb and 4.3-fold for ARH. (LLM, conf=0.95)

  cites Tao et al., 2014 source

In the paper

“Studies in cultured cells suggested a role of Dab2 in endocytic recycling and trafficking of integrins and thus impact cell mobility”

What the sources say

• ?Not checked — no full text of the sourcecites Caswell et al., 2009 source
• Partly supported

  The Results (section 3.3; page unavailable) show that DAB2 acts with AP-2 in activated β1-integrin endocytosis and that their combined knockdown impairs cell migration. The same section suggests a role for clathrin in integrin delivery or recycling, but does not establish that DAB2 mediates recycling. (LLM, conf=0.88)

  cites Chao and Kunz, 2009 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Chetrit et al., 2009 source

In the paper

“Mammary glands/epithelia | Delayed involution”

• Also stated in: § Roles of Dab2 in mammary involution · boosted

  “The most robust phenotype of Dab2 null mammary glands is a transient delay in mammary involution (Tao et al., 2014).”

What the sources say

• Supported

  The Results section, under “Delayed mammary involution in Dab2 conditional knockout mice,” reports consistently delayed mammary regression in Dab2-deficient mice compared with controls. It describes the delay as transient: differences were minimal by day 5. (LLM, conf=0.94)

  cites Tao et al., 2014 source

In the paper

“Tumors/multiple types | Uterine hyperproliferation, Ovarian epithelial growth, Increased tumor incidence”

What the sources say

• ?Not checked — no full text of the sourcecites Yang et al., 2006 source
• Partly supported

  The Results (Characterization of dab2 conditional mutant mice; page unavailable) report an increased incidence of preneoplastic lesions, including in the uterus, in aged mice with Dab2 deletion. They do not specifically report uterine hyperproliferation, and the surviving adult mice had conditional, mosaic deletion rather than constitutive Dab2-null status. (LLM, conf=0.86)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“Additionally, a suppressive activity of Dab2 was observed on the MAPK downstream effector, the expression of c-Fos”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites He et al., 2001
• Supported

  In the section on Dab2 transfection and c-Fos expression, the authors report that Dab2 expression inhibited serum-stimulated c-Fos expression in F9 cells (Fig. 6B). They also report reduced c-Fos expression in Dab2-expressing PA-1 cells despite unaffected MAPK activation (Fig. 6C). (LLM, conf=0.94)

  cites Smith et al., 2001 source
• Supported

  The Results section, “Dab2 Down Regulation Enhances c-Fos Expression in Differentiated Embryonic Stem Cells” (page not provided), reports that suppressing Dab2 restored c-Fos expression. The Introduction identifies c-Fos transcriptional activation as a target downstream of MAPK, while the Discussion says the study supports Dab2’s regulation of c-Fos in vivo. (LLM, conf=0.94)

  cites Yang et al., 2009 source

In the paper

“Thus, its functions in mediating polarized trafficking of cell adhesion molecules such as integrins and E-cadherin provide possible mechanisms for failure in endoderm epithelial polarity, sorting, and organization of Dab2 deleted embryos”

What the sources say

• Partly supported

  The Discussion and Figure 6 describe Dab2-dependent E-cadherin trafficking as a proposed mechanism for epithelial polarity and surface positioning; the figure links loss of polarity to disorganization of Dab2-deficient endoderm cells. The paper mentions integrins as adhesion molecules, but the passages do not establish Dab2-mediated polarized trafficking of integrins. (LLM, conf=0.86)

  cites Yang et al., 2007 sourceExperimental — accuracy not yet measured
• Supported

  The Background identifies polarized trafficking of integrins and E-cadherin as a possible explanation for Dab2’s role in epithelial polarity and organization. The Discussion section on epithelial organization links Dab2 deletion to reduced trafficking of cell-surface adhesion molecules, impaired polarity, and failure of primitive endoderm cells to position at the surface. The claim preserves the paper’s proposed-mechanism framing. (LLM, conf=0.93)

  cites Moore et al., 2013 source

In the paper

“Compensatory expression and partial functional redundancy by numb and Arh have been noted in Dab2 knockout mice (Moore et al., 2013; Tao et al., 2014, 2016a).”

What the sources say

• Partly supported

  The Results report elevated Numb and Arh expression in Dab2-deleted E9.5 embryos, supporting compensatory expression. The Results also propose that these proteins may partly substitute for Dab2, but say that further deletion or overexpression experiments are needed to test functional rescue; partial functional redundancy was therefore suggested, not established. (LLM, conf=0.88)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Tao et al., 2014, 2016a

In the paper

“LRP2/Megalin was one of the first endocytic cargos identified for the Dab2 adaptor (Oleinikov et al., 2000; Yang et al., 2002a)”

What the sources say

• Supported

  The Introduction identifies gp600/megalin as LRP-2 and calls it the first known transmembrane receptor to interact with Dab2. The discussion identifies it as an endocytic receptor and an intracellular partner of Dab2, supporting its identification as an early Dab2-associated endocytic cargo. The paper proposes, but does not establish, a role for Dab2 in its trafficking. (LLM, conf=0.89)

  cites Oleinikov et al., 2000 source
• Supported

  In “Function of Disabled-2 in the Megalin Endocytic Pathway” (page unavailable), the paper reports that Dab2 selectively binds peptides from megalin’s intracellular domain. The Discussion identifies megalin as an endocytic cell-surface receptor associated with Dab2, supporting the citing sentence’s characterization. (LLM, conf=0.87)

  cites Yang et al., 2002a source

In the paper

“Kidney/proximal convoluted tubule epithelia | Mild proteinuria”

• Also stated in: § Roles of Dab2 in kidney: protein re-uptake · plain

  “Indeed, Dab2 null mice have a mild proteinuria (Morris et al., 2002b; Moore et al., 2013).”

What the sources say

• Supported

  The kidney-function section reports that conditionally null Dab2 mice excrete DBP, RBP and other proteins in their urine, while total urinary protein was not systematically altered. The transport-function section describes these mice as less severely affected than megalin-null mice, consistent with the claim’s description of mild proteinuria. The mice studied for this finding were conditionally null. (LLM, conf=0.88)

  cites Morris et al., 2002b source
• Partly supported

  The Results section (“Role of Dab2 in cholesterol metabolism in vivo”) reports mild proteinuria in Dab2-deficient mice with a Sox2-Cre conditional deletion. It does not establish this phenotype in constitutive Dab2-null mice; the Results section on constitutive null embryos reports that they die early in development. (LLM, conf=0.87)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“The study concludes that the combination of Arh and Dab2 is responsible for the majority of adaptor functions in LDLR endocytosis and LDLR-mediated cholesterol homeostasis.”

What the sources say

• Supported

  The Discussion explicitly concludes that the concerted roles of Arh and Dab2 account for the majority of adaptor function in LDLR endocytosis, circulating-cholesterol clearance, and regulation of cholesterol synthesis. This matches the attributed conclusion about LDLR-mediated cholesterol homeostasis. (LLM, conf=0.95)

  cites Tao et al., 2016a source

In the paper

“When Sox2-Cre is used to delete Dab2 gene in the cre-lox conditional knockout mice to bypass the its role in early embryogenesis (Yang et al., 2002a, 2007), live mice are produced (Moore et al., 2013).”

What the sources say

• Supported

  In Results, under “Characterization of dab2 conditional mutant mice” (page not provided), the paper reports that Sox2-Cre conditional Dab2 knockouts were produced at a Mendelian ratio and that adult mutants were fertile. It also explains that Sox2-Cre deletes Dab2 in the embryo proper while sparing extraembryonic tissues, supporting the described conditional-knockout approach. (LLM, conf=0.94)

  cites Moore et al., 2013 source

In the paper

“The aged Dab2 null mice have higher frequency of tumors upon dissection, observed mainly in the uterus, ovary, liver, mammary gland, and colon, similar to the previous report for the dab2 heterozygous mice (Yang et al., 2006; Moore et al., 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Yang et al., 2006 source
• Partly supported

  In Results, under “Characterization of dab2 conditional mutant mice” (page not provided), the paper reports an increased incidence of preneoplastic lesions in aged mice, mainly in the uterus, ovary, mammary gland, and colon. It does not report tumors at those sites or include the liver; it says the tumor phenotypes will be reported elsewhere. (LLM, conf=0.91)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“In adipose tissues, Dab2 is found to express in pericytes attached to the vascular structures (Tao et al., 2016b).”

What the sources say

• Supported

  The Results section (‘Dab2 is essential for adipose differentiation of cells of the stromal vascular fractions,’ Fig. 6a; page not provided) reports Dab2-positive cells surrounding blood vessels in adipose tissue. It estimates that about 20% of the pericytes immediately surrounding vascular structures are Dab2-positive. (LLM, conf=0.94)

  cites Tao et al., 2016b source

In the paper

“though no increased tumor incidence was reported in the characterization of a Dab2 conditional knockout line (using Meox2-Cre; Morris et al., 2002b).”

What the sources say

• Supported

  The “Rescue of Dab2-deficient embryos” section describes generating conditionally null mice using Meox2-Cre. The “Dab2 and cancer” section states that the authors had not detected increased tumor incidence in their conditionally null mice. This supports the citing sentence’s careful wording that no increase was reported, rather than claiming that a later increase was ruled out. (LLM, conf=0.95)

  cites Morris et al., 2002b source

In the paper

“For another Dab2 conditional line produced more recently, increases in incidence of tumors and preneoplastic lesions were noticed (Moore et al., 2013).”

What the sources say

• Partly supported

  In Results, under “Characterization of dab2 conditional mutant mice” (page unavailable), the authors report an increased incidence of preneoplastic lesions in aged mice from their conditional line. They do not report an increased incidence of tumors; they say studies of tumor phenotypes will be reported elsewhere. (LLM, conf=0.90)

  cites Moore et al., 2013 sourceExperimental — accuracy not yet measured

In the paper

“The remarkable difference in resistance to high caloric diet-induced weight gain of the dab2-deleted mice was present only in juvenile but not in mature mice (Tao et al., 2016b).”

What the sources say

• Supported

  The Results section reports that Dab2-null mice resisted high-fat-diet-induced weight gain when the diet began at 3 weeks to 3 months of age, but showed no difference from controls when it began at 6 months. The Discussion likewise says the effect was observed only in young mice, not older mice. (LLM, conf=0.95)

  cites Tao et al., 2016b source

In the paper

“The tumor suppressor functions of Dab2 have been attributed to its roles in suppressing Ras/MAPK signaling (He et al., 2001; Zhou and Hsieh, 2001)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites He et al., 2001
• Supported

  The Abstract describes DOC-2/DAB2 as a potential tumor suppressor and reports that it interrupts Grb2–SOS binding, suppressing downstream ERK activation. The Discussion identifies this as an inhibitory effect on the Ras-mediated MAP kinase pathway, supporting the attributed mechanism. (LLM, conf=0.91)

  cites Zhou and Hsieh, 2001 source

In the paper

“From epidemiological studies, pregnancy and lactation at early age is known to have a small protective effect against breast cancer (Kelsey and Gammon, 1991).”

What the sources say

• ?Could not verify

  No passage from our copy matched the claim. Searches for early pregnancy, age at first birth, lactation, and breastfeeding returned no passages, so the claimed protective effect cannot be verified from our copy. (LLM, conf=0.70)

  cites Kelsey and Gammon, 1991 sourceExperimental — accuracy not yet measured

In the paper

“Based on analyses of cell lines and primary stromal mesenchymal stem cells and cells of the adipose vascular stromal fraction, the mechanism was determined to be a requirement of Dab2 in adipocyte differentiation (Figure 4; Tao et al., 2016b).”

What the sources say

• Supported

  The Results section on stromal vascular fraction cells reports adipogenic differentiation in approximately 12% of Dab2-expressing control cells versus fewer than 1% of Dab2 knockout cells, and concludes that Dab2 is required for differentiation of a pre-adipocyte population. The Results also report reduced adipogenic activity after Dab2 suppression in cell-line assays, supporting the citing sentence's summary of the cell analyses. (LLM, conf=0.92)

  cites Tao et al., 2016b source

In the paper

“In the pre-adipocytes, Dab2 is required to suppress the activity of Ras/MAPK”

What the sources say

• Supported

  The Discussion states that Dab2 suppresses Ras/MAPK signaling and is essential for suppressing the pathway during adipocyte differentiation. The Results report that Erk1/2 activation remained elevated in Dab2-null cells, supporting the claim in the pre-adipocyte differentiation context. Page numbers were not supplied. (LLM, conf=0.94)

  cites Tao et al., 2016b source

In the paper

“and the adipose lineage Dab2-deleted (using aP2-Cre) mice have essentially the same levels of serum glucose, lipids, and other metabolites as wildtypes.”

What the sources say

• Partly supported

  The Results section on adipose cell number (page not provided) says serum lipid profiles were indistinguishable between mice with and without aP2-Cre-mediated Dab2 deletion. It identifies the comparison group as heterozygous controls, not wildtypes, and does not report comparable glucose or other metabolite levels for the aP2-Cre mice. The glucose findings elsewhere in Results concern Sox2-Cre Dab2-null mice. (LLM, conf=0.88)

  cites Tao et al., 2016b sourceExperimental — accuracy not yet measured

In the paper

“Restricted Dab2 deletion in adipose lineage using aP2-Cre supports that this phenotype is adipocyte cell autonomous”

What the sources say

• Supported

  In the Results section on adipocyte differentiation (page not provided), the authors explicitly say that aP2-Cre lineage-restricted Dab2 deletion and reduced weight gain suggest a cell-autonomous requirement for Dab2 in adipocyte development. The Results also report reduced high-fat-diet weight gain in mice with adipose-restricted deletion, matching the citing sentence’s qualified claim that this finding supports cell autonomy. (LLM, conf=0.94)

  cites Tao et al., 2016b source

In the paper

“and cell adhesion/migration (Chetrit et al., 2009; Chao and Kunz, 2009; Chetrit et al., 2009; Teckchandani et al., 2009; Xie et al., 2015).”

What the sources say

• ?Not checked — no full text of the sourcecites Chetrit et al., 2009 source
• Partly supported

  The Results (§3.3; page not provided) show that DAB2 helps regulate focal adhesion disassembly and that combined DAB2/AP-2 knockdown inhibits cell migration. The paper does not attribute DAB2’s tumor-suppressor function to its role in adhesion or migration. (LLM, conf=0.86)

  cites Chao and Kunz, 2009 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results report that removing Dab2 inhibited HeLa cell migration on collagen IV, supporting a role in migration. But the Introduction says it is unclear whether Dab2’s roles in cancer and migration share a mechanism, and the Discussion considers an effect on adhesion unlikely to explain its migration result. The paper therefore does not establish that Dab2’s tumor-suppressor function is attributable to adhesion or migration. (LLM, conf=0.85)

  cites Teckchandani et al., 2009 sourceExperimental — accuracy not yet measured

In the paper

“The research results suggest Dab2 is essential for the expansion of adipocyte cell number.”

What the sources say

• Partly supported

  The Results section reports fewer adipocytes in Dab2-deficient mice fed a high-fat diet, supporting a role for Dab2 in cell-number expansion. The Discussion limits this effect to young mice and says older mice did not differ from controls in their response to the diet; the claim omits those age and diet conditions. (LLM, conf=0.87)

  cites Tao et al., 2016b sourceExperimental — accuracy not yet measured

In the paper

“In, Dab2 is seen highly expressed in extraembryonic tissues (placenta) during development.”

In the paper

“Nevertheless, tumor incidence is relatively low (about 10%)”

In the paper

“The studies of mutant mice established that Dab2 plays multiple physiological roles through its endocytic functions and modulation of signal pathways.”

In the paper

“cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins”

In the paper

“more recent investigation of the Dab2-deficient mice revealed several phenotypes, which can be accounted for by several previously suggested mechanisms”

In the paper

“Probably, the activity as a negative regulator of the Ras/MAPK pathway contributes to the tumor suppressor activity of Dab2 as well.”

In the paper

“In addition, Dab2 has feature of an signaling adaptor, as the C-terminal part of the protein contains a proline-rich domain that mediates the association of Dab2 with additional proteins, such as Grb2, Src, and Fyn”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 1998

In the paper

“Through its functions in endocytosis of signaling components such as Axin or LRP6, Dab2 is also suggested to plays roles in the regulation of the Wnt pathways”

What the sources say

• ?Not checked — no full text of the sourcecites Hocevar et al., 2003 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Jiang et al., 2008, 2009, 2012

In the paper

“Since the two SH3 domains of Grb2 bind competitively to both Sos1 and Dab2, to their proline-rich motifs, expression levels and phosphorylation of Dab2 and Sos1 modulate the abundance of Sos1/Grb2 complexes.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 1998

In the paper

“megalin/Dab2 mediated protein re-uptake in the proximal tubule cells is an likely physiological function of Dab2 in kidney”

In the paper

“The hormonal regulation of Dab2 expression in mammary epithelial cells is unique, since the expression was not seen to be significantly altered by sterol hormones in other tissues or cell types.”

In the paper

“As expected, physiological phenotypes in the Dab2 conditional knockout mice have been observed in many of these tissues or cell types that have high Dab2 expression in wild-type mice”

In the paper

“Deletion of Dab2 in zebrafish embryos through Cas9 mutagenesis resulted in a significant reduction in cardiomyocyte number (Hofsteen et al., 2016)”

What the sources say

• ?Not checked — no full text of the sourcecites Hofsteen et al., 2016 source

In the paper

“In cell culture studies, Dab2 also was shown to modulate several signaling pathways.”

In the paper

“The members of the LDL (low density lipoprotein) receptor family contain the NPXY motif(s) specifically recognized by Dab2”

What the sources say

• ?Not checked — no full text of the sourcecites Willnow et al., 1999 source
• ?Not checked — no full text of the sourcecites Herz et al., 2000 source
• ?Not checked — no full text of the sourcecites Hussain, 2001 source

In the paper

“At the N-terminus, Dab2 possesses a PTB/PID domain that can bind an NPXY (Asn-Pro-X-Tyr, X represents any amino acid) motif found in a subset of cell surface receptors (Bork and Margolis, 1995).”

What the sources say

• ?Not checked — no full text of the sourcecites Bork and Margolis, 1995 source

In the paper

“Among the mouse tissues surveyed, the lactating mammary gland has relatively high Dab2 expression (Figure 2).”

In the paper

“an increase in total Erk1/2 activity was observed in the total embryonic lysate of E9.5 Dab2 null embryos (Smith et al., submitted)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Smith et al., submitted

In the paper

“suggesting Dab2 has a physiological role in the fine-tuning of the Ras/MAPK pathway”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Smith et al., submitted

In the paper

“Adipose/Adipocytes/pericytes | Resistant to induced adipogenesis”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Tao et al., 2016b source

In the paper

“Thus, Dab2 links clathrin-coated cargos containing transmembrane proteins with an NPXY motif to the myosin motor, facilitating their endocytosis and directional trafficking”

What the sources say

• ?Not checked — no full text of the sourcecites Morris et al., 2002a source
• ?Not checked — no full text of the sourcecites Hasson, 2003 source

In the paper

“The Dab2 proline-rich domain (PRD) at C-terminus contains multiple stretches of poly-proline motifs that resemble those in Sos1, a guanine nucleotide exchange factor for and activator of Ras”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Xu et al., 1998

In the paper

“The C-terminus binds to the myosin VI motor protein (Inoue et al., 2002; Morris et al., 2002a; Hasson, 2003; Spudich et al., 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Inoue et al., 2002 source
• ?Not checked — no full text of the sourcecites Morris et al., 2002a source
• ?Not checked — no full text of the sourcecites Hasson, 2003 source

In the paper

“Immune system/Treg | No obvious phenotype in vivo; failed to suppress T cells”

• Also stated in: § Roles of Dab2 in immune cells · plain

  “In in vitro assay, Dab2-restricted knockout of Treg cells failed to suppress the proliferation of responder T cells.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Jain et al., 2009 source

In the paper

“Deletion of Dab2 gene in mice only results in a small increase of serum cholesterol level (Moore et al., 2013)”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Moore et al., 2013 source

In the paper

“The redundant function of Arh with Dab2 may account for the very mild kidney functional defect in the Dab2 null mice (Nagai et al., 2003).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Nagai et al., 2003 source

In the paper

“To date, Dab2 expression has been reported to be reduced or lost in many additional cancer types, including colon (Kleeff et al., 2002), prostate (Tseng et al., 1998), esophageal (Anupam et al., 2006), nasopharyngeal (Tong et al., 2010), and head and neck (Hannigan et al., 2010).”

What the sources say

• ?Not checked — no full text of the sourcecites Kleeff et al., 2002 source
• ?Not checked — no full text of the sourcecites Tseng et al., 1998 source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Anupam et al., 2006 source

In the paper

“suggesting Dab2 is not required for embryonic development of adipose tissues”

In the paper

“The phenotypic characterization of the Dab2 null mice has revealed how endocytosis may impact the physiological functions in intact animals (Table 1).”

In the paper

“So far, the observed physiological functions can be accounted for by the cellular function of Dab2 in endocytosis: substrate uptake and modulation of signaling pathway (especially Ras/MAPK pathway).”

In the paper

“Dab2 gene deletion was reported to affect regulatory T cell (Treg) function (Jain et al., 2009).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Jain et al., 2009 source

In the paper

“Several subsequent reports corroborated loss or a reduced Dab2 expression in human breast cancer (Sheng et al., 2000b; Bagadi et al., 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Sheng et al., 2000b source
• ?Not checked — no full text of the sourcecites Bagadi et al., 2007 source

In the paper

“The link of Dab2 to oncogenesis was first made in a differential expression screening experiment, in which a short mRNA fragment was identified as DOC-2 (differentially expressed in ovarian cancer, known as Dab2 at a later time), and the mRNA was found lost in ovarian cancer (Mok et al., 1994).”

What the sources say

• ?Not checked — no full text of the sourcecites Mok et al., 1994 source

In the paper

“epithelial organization (Sheng et al., 2000b; Yang et al., 2002b, 2007)”

What the sources say

• ?Not checked — no full text of the sourcecites Sheng et al., 2000b source
• ?Not checked — no full text of the sourcecites Yang et al., 2002b source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Yang et al., 2007 source

In the paper

“Redundancy with similar adaptors, especially Arh and numb that are expressed in the same cell types, may obscure the physiological impacts and roles of Dab2.”

In the paper

“Another early support was the identification of Dab2 as a suppressed gene in carcinogen-induced mammary tumors in rodents (Schwahn and Medina, 1998).”

What the sources say

• ?Not checked — no full text of the sourcecites Schwahn and Medina, 1998 source

In the paper

“Thus, the induction of Dab2 expression may contribute to the protection against breast cancer risk that pregnancy and lactation may offer.”

In the paper

“and its function is required for early embryonic development.”

In the paper

“which otherwise phosphorylates the adipogenic master regulator PPARγ and prevents its adipogenic function (Tao et al., 2016b).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Tao et al., 2016b source

In the paper

“Interestingly, the Dab2 null mice are nearly indistinguishable from wildtype mice after birth and when been fed a regular chow diet”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Tao et al., 2016b source

In the paper

“In a high fat and caloric feeding experiment that was to investigate cholesterol metabolism, an unexpected observation was that the Dab2 null mice were resistant to high fat diet-induced weight gain (Tao et al., 2016b).”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites Tao et al., 2016b source

In the paper

“Although Dab2 is a nonessential gene following completion of development”

In the paper

“Based on the cellular study of Dab2 functions in the endocytosis of LRP1 and LRP2 (megalin), integrins, TGF-beta signaling pathway, Wnt pathway, etc, some additional phenotypes are expected, but those are either not found or not significant in whole mice.”