Differential requirement for Dab2 in the development of embryonic and extra-embryonic tissues

Dab2 null mice show ovarian epithelial growth.

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

Dab2 null mice are produced at an expected ratio and are essentially phenotypically normal in unchallenged conditions.

“Dab2 null mice are produced at an expected ratio and the mice are essentially phenotypically normal in unchallenged conditions (Moore et al., 2013).”

The involvement of Dab2 in cholesterol metabolism in intact animals is uncertain.

“the involvement of Dab2 in cholesterol metabolism in intact animals is uncertain”

The impact of Dab2 deletion on cardiac development is not notable.

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

Dab2 null mice show uterine hyperproliferation.

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

Compensatory expression and partial functional redundancy by Numb and Arh have been noted in Dab2 knockout mice.

“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).”

Another more recent Dab2 conditional line showed increases in incidence of tumors and preneoplastic lesions.

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

Sox2-Cre is expressed in the inner cell mass and deletes Dab2 in a mosaic fashion, and the embryo proper is essentially depleted of Dab2 allele by E9.5.

“Sox2-Cre is expressed in the inner cell mass and delete Dab2 gene in a mosaic fashion, and the embryo proper is essentially depleted of Dab2 allele by E9.5 (Moore et al., 2013).”

Aged Dab2 null mice have higher frequency of tumors upon dissection, mainly in the uterus, ovary, liver, mammary gland, and colon.

“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).”

Dab2 null mice show increased serum cholesterol.

“Liver/sinusoidal endothelial cells | Increased serum cholesterol”

Dab2's 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.

“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”

When Sox2-Cre is used to delete Dab2 in cre-lox conditional knockout mice to bypass its role in early embryogenesis, live mice are produced.

“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).”

dab2 (fl/df):Sox2-Cre mice are conditional knockouts that are essentially Dab2 null after birth.

“dab2 (fl/df):Sox2-Cre were conditional knockouts shown to be essentially Dab2 null after birth”

Dab2 null mice show mild proteinuria.

“Kidney/proximal convoluted tubule epithelia | Mild proteinuria”

Dab2 functions in endocytic trafficking to sustain cell polarity and epithelial organization; loss of Dab2 leads to endoderm epithelial disorganization and embryonic failure.

“Therefore, Dab2 functions in endocytic trafficking to sustain cell polarity and thus epithelial organization, and hence loss of Dab2 leads to endoderm epithelial disorganization and failure of the embryos”

Dab2 null mice show increased tumor incidence.

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

In dab2-deficient embryos, extra-embryonic endoderm cells are present but fail to sort and form primitive and subsequent visceral endoderm epithelia, and intermingle with ectoderm cells.

“In the dab2-deficient embryos, extra-embryonic endoderm cells are present but fail to sort and form primitive and subsequent visceral endoderm epithelia. Rather, the extra-embryonic endoderm cells intermingle with the ectoderm cells”

Dab2 is critical for surface targeting and restriction of cell adhesion molecules and the establishment and maintenance of epithelial polarity.

“Analyses in embryoid bodies and cultured cells support that Dab2 is critical for the surface targeting and restriction of cell adhesion molecules and the establishment and maintenance of epithelial polarity”

Dab2 null mice show failed cell sorting in blastocysts/primitive and extraembryonic endoderm early embryos.

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

Deletion of the Dab2 gene in mice only results in a small increase of serum cholesterol level.

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

Kidney was confirmed to be one of the highest expressing tissues profiled from a large public expression database, and the expressing cells are kidney epithelial cells lining the proximal convoluted tubule.

“kidney was confirmed to be one of the highest expressing tissues profiled from a large public expression database (Figure 2), and the expressing cells was found later to be the kidney epithelial cells lining the proximal convoluted tubule (Moore et al., 2013).”

Dab2-deficient mice have only minor changes in serum cholesterol level.

“Dab2-deficient mice have only minor changes in serum cholesterol level”