The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index; 12 of the 24 sources its claims cite were checked for support.
Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis
Open accessAbstract
The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr-5 weeks posttransplant. Using FACS analysis, both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient. In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks. This transparent adult zebrafish serves as the ideal combination of both sensitivity and resolution for in vivo stem cell analyses.
Overview
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Written from the paper’s full text.
TL;DR
White et al. generated a doubly mutant zebrafish line, *casper* (*nacre*;*roy*), that lacks melanocytes and iridophores and is transparent throughout adulthood, enabling in vivo visualization of transplanted hematopoietic and tumor cells. Using this line, they tracked HSPC engraftment to the kidney marrow and detected melanoma engraftment and distant metastasis far earlier than in wild-type recipients.
Key findings
- *casper* fish (homozygous *nacre* and *roy*) completely lack melanocytes and iridophores in embryogenesis and adulthood; organs including heart, intestinal tube, liver, and gallbladder are visible by standard stereomicroscopy, and ventricular contraction can be observed. The line is viable, with incrossed adults producing offspring at expected Mendelian ratios and no heterozygous phenotype.
- After intracardiac transplantation of 100,000 beta-actin:GFP whole kidney marrow cells into a 25 Gy–irradiated *casper* recipient, GFP-labeled cells were visible in the kidney region and gill vasculature by 2 weeks and largely confined to the kidney by 4 weeks; FACS showed equal multilineage engraftment in *casper* and wild-type recipients, but only *casper* allowed visualization. Anti-GFP IHC confirmed homing of donor cells to kidney marrow.
- Confocal imaging of transplanted *casper* fish resolved single cells and clusters at ~5 μm, with a maximal depth of field of 88 μm from the skin surface; no discernible GFP signal was obtainable in wild-type recipients.
- In tumor transplants, 200,000 disaggregated NRAS-GFP or BRAF;p53 melanoma cells injected IP or intracardiac produced visible tumor masses within 5 days in *casper*, versus 2–3 weeks in wild-type; 9/24 (37.5%) of BRAF;p53 recipients showed distant metastasis between 5 and 28 days, peaking at 5–10 days, with one tumor volume measured at 1496 mm³ by 3D calculation.
Methods
- Design: generation and characterization of a compound pigmentation mutant zebrafish line, followed by transplantation assays for hematopoietic and tumor cells.
- Sample/data: wild-type (AB), tg(beta-actin:GFP), *roy orbison*, *panther/rose*, *nacre*, *golden*, *albino*, and p53 lines; tg(mitf:NRAS-GFP) and tg(mitf:BRAF) melanoma donors crossed to p53−/−. Recipients irradiated with 25 Gy two days before transplant; 5 μl of 100,000 cells/μl marrow or 50,000 cells/μl tumor suspension injected intracardially or intraperitoneally.
- Analysis: stereomicroscopy (Zeiss Discovery V8), confocal microscopy (Zeiss LSM Meta), H&E and Masson's trichrome histology, anti-GFP immunohistochemistry, and FACS of kidney marrow for forward/side scatter and GFP.
Limitations
- Stated: the line requires both mutations in the homozygous state, needing at least two breeding cycles to use existing transgenic lines; the *roy* mutation is unknown, so it may affect unknown aspects of tumor or stem cell biology (though it does not affect survival); imaging very deep tissues may require multiphoton microscopy, which is experimental in zebrafish.
- Evident from the text: the metastasis mechanism is described as unclear, and the authors note the early dissemination may reflect accumulated genetic changes in donor tumors present for over a month; the tumor volume of 1496 mm³ is reported for a single representative fish.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
12 of 24 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish.”
What the sources say
- Partly supportedcites Burns et al., 2005 sourceExperimental — accuracy not yet measured
The paper’s Abstract describes zebrafish experiments on normal hematopoietic stem-cell specification and maintenance during development and adulthood. It does not establish zebrafish as a model for understanding cancer stem cells; searches for cancer stem cells, leukemia, and tumors found no such discussion in the paper’s body. (LLM, conf=0.86)
- Not matchedcites Traver et al., 2004a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Langenau et al., 2007 sourceExperimental — accuracy not yet measured
In “Identifying the cancer stem cell in zERMS” (page unavailable), the paper uses zebrafish to isolate an ERMS cancer stem cell and compares it with normal muscle satellite cells. This supports the model’s usefulness for studying cancer stem cells, but the paper does not directly establish its usefulness for studying normal stem cells. (LLM, conf=0.82)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most strikingly, the body of the fish is almost entirely transparent.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of these organs are easily visible in any of the other pigment mutants studied (see Figure S1 available online) other than the heart and intestinal tube in rose.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr–5 weeks posttransplant.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Examination of the cardiac region of the casper mutant (Movie S1) shows that ventricular contraction can be observed, making this mutant useful for in vivo analysis of genetic perturbations in cardiac function.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In female adults, individual eggs are easily observable, as seen in Figure 1D.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This line, which we have named casper for its ghost like appearance, demonstrates a complete lack of all melanocytes and iridophores in both embryogenesis and adulthood.”
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Organs that can be seen using standard stereomicroscopy in casper include the heart, intestinal tube, liver, and gallbladder.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain tissue is visible to a small extent.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 16
- It may state two separate claims as one. 29
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“In addition, bioluminescence has met with only limited success in the zebrafish system (Creton et al., 1997; Kaneko and Cahill, 2005”
What the sources say
- Not checked — no full text of the sourcecites Creton et al., 1997 source
- Disputedcites Kaneko and Cahill, 2005 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes the authors’ bioluminescent transgenic zebrafish as a high-throughput system for studying circadian gene expression in whole animals, contrary to the broad claim of only limited success. It notes a narrower limitation: embryos were unsuitable for circadian studies with these lines, whereas older larvae produced robust rhythms. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Prior work from our laboratory has demonstrated that the zebrafish is a useful model for understanding the genetics of both HSPC (Burns et al., 2005; Traver et al., 2004a”
What the sources say
- Supportedcites Burns et al., 2005 source
The citation is attached to the HSPC portion of the citing sentence. In the section on Mind bomb and HSC specification, the paper uses zebrafish mutants to investigate genes controlling hematopoietic stem and progenitor cells, supporting zebrafish as a model for that purpose. The supplied sentence does not attach this citation to tumor stem cell biology. (LLM, conf=0.91)
- Not matchedcites Traver et al., 2004a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Langenau et al., 2007 source
The section ‘Identifying the cancer stem cell in zERMS’ reports that zebrafish experiments isolated a cancer stem cell and helped identify pathways relevant to its self-renewal. This supports the tumor-stem-cell part attributed to this paper; the printed sentence cites Burns and Traver for HSPCs. (LLM, conf=0.91)
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The characteristic adult pigmentation pattern of the zebrafish consists of three distinct classes of pigment cells arranged in stripes (Figure 1A): black melanophores, reflective iridophores, and yellow xanthophores”
What the sources say
- Supportedcites Rawls et al., 2001 source
The “Zebrafish Melanocyte Development” section names yellow xanthophores, reflective iridophores, and black melanocytes, noting that melanocytes are also called melanophores. “Simple Models of Organogenesis” discusses all three cell types in relation to adult body stripes. (LLM, conf=0.91)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In vivo imaging is a critical counterpart to studying molecular processes in cell culture systems (Koo et al., 2006”
What the sources say
- Supportedcites Koo et al., 2006 source
The abstract (p. 1) calls in vivo molecular imaging an “essential bridge between in vitro data and their translation into clinical applications.” The Introduction (p. 1) also describes its use in studying molecular and cellular mechanisms in animal models. Together, these support the claim’s characterization of in vivo imaging as a critical counterpart to in vitro study. (LLM, conf=0.89)
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“MRI is a useful technique for visualizing transplanted cells in vivo and has a spatial resolution of 25–50 μm but requires a significant amount of magnetic dye treatment of transplanted cells, has limited sensitivity, and requires considerably complex and expensive equipment (Lee et al., 2007; Lyons, 2005”
What the sources say
- Not checked — no full text of the sourcecites Lee et al., 2007 source
- Partly supportedcites Lyons, 2005 sourceExperimental — accuracy not yet measured
Table 1 (Conclusions; page not provided) supports MRI's high spatial resolution and low sensitivity, but gives a resolution of 25–100 μm, not 25–50 μm. The MRI imaging section describes contrast probes, not a requirement for substantial magnetic-dye treatment of transplanted cells. The paper notes that equipment costs vary between modalities but does not specifically describe MRI equipment as complex and expensive. (LLM, conf=0.90)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Bioluminescence has been utilized to detect engraftment and hematopoietic reconstitution after transplantation of luciferase-positive HSC populations (Welsh and Kay, 2005; Cao et al., 2006”
What the sources say
- Not checked — no full text of the sourcecites Welsh and Kay, 2005 source
- Partly supportedcites Cao et al., 2006 sourceExperimental — accuracy not yet measured
The Results (page not provided) report using bioluminescence to assess engraftment after transplantation of luciferase-expressing embryonic stem cells into rat hearts. The source does not report transplantation of hematopoietic stem cell (HSC) populations or detection of hematopoietic reconstitution. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Another concern is the dose of radiation in both CT and PET that would need to be delivered to the fish to achieve adequate resolution, which may have independent biological effects (Paulus et al., 2000; Pickhardt et al., 2005”
What the sources say
- Partly supportedcites Paulus et al., 2000 sourceExperimental — accuracy not yet measured
The Radiation Dose section calls radiation exposure an important concern in microCT studies and compares the estimated dose in mice with published lethal-dose values; Table 1 reports organ doses for high-resolution and screening scans. This supports a concern about CT radiation, but the paper does not establish the dose needed for adequate resolution in fish or address biological effects from PET imaging. (LLM, conf=0.82)
- Partly supportedcites Pickhardt et al., 2005 sourceExperimental — accuracy not yet measured
The Discussion says radiation from microCT scanning could potentially affect tumor growth and interfere with serial monitoring in mice. Materials and Methods says the authors chose parameters that provided adequate resolution while minimizing radiation dose. The paper does not establish this concern for PET or fish. (LLM, conf=0.88)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The iridophores of the skin are a dermal-hypodermal structure which are normally intimately connected to the surrounding xanthophores and lie just above the trunk skeletal muscle”
What the sources say
- Partly supportedcites Le Guellec et al., 2004 sourceExperimental — accuracy not yet measured
In “An overview of the current knowledge of fish skin” (page unavailable), the paper places iridophores and xanthophores in the hypodermis, between the dermis and underlying muscle. It does not say that iridophores are normally intimately connected to xanthophores, or specifically describe iridophores as a dermal-hypodermal structure. (LLM, conf=0.84)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
In the paper
“However, there is a complete absence of the scleral iridophore layer (Figure 2A, arrow), which is demonstrated by the loss of refractive crystalline plates (Clothier and Lythgoe, 1987”
What the sources say
- Not checked — no full text of the sourcecites Clothier and Lythgoe, 1987 source
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The gross morphology of the casper eye is normal, with maintenance of the scleral-corneal border and normal pigmented retinal epithelial cells.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In wild-type animals, the pigmented retinal epithelium is normally obscured by the reflective iridophores; their absence in roy mutants exposes the black cells across the entire surface of the eye.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The roy orbison (roy) zebrafish (Figure 1C) is a spontaneous mutant and has a complete lack of iridophores, uniformly pigmented eyes, sparse melanocytes, and a translucency of the skin.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The casper mutant is entirely viable, with incrossed adults producing large numbers of viable offspring at expected mendelian ratios and no heterozygous phenotype.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although no GFP can be visualized with a fluorescent stereoscope in the wild-type, a normal distribution of hematopoietic cells is seen at 4 weeks posttransplant, and many of these cells are GFP positive (Figure 3B, top).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The pattern of engraftment at 5 days in the intracardiac recipients of NRAS-GFP cells (Figure 4A, bottom) largely reflects local deposition of tumor cells along the transplantation tract, although some cells can be seen migrating dorsally.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In a similarly transplanted wild-type fish, no visible tumors are seen until 2 to 3 weeks posttransplant, and metastatic cells are not detectable.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Figure 4C, this individual fish is fully viable over this period of time, and the tumor volume can be assessed at each time point without sacrificing the animal.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At 4 hr posttransplant, a pool of blood surrounds the cardiac chambers, which likely represents extravasated blood in the pericardial sac.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All of the hematopoietic cells are strongly GFP-positive by IHC (Figure 3C, right, brown staining), whereas none of the kidney tubule cells stain for GFP.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inset of Figure 4A (bottom) demonstrates that the tumor cells (taken at 10 days posttransplant) continue to be strongly GFP positive and indicates that they could be localized even in the absence of black pigmentation.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mediolateral and ventral views of this tumor allow for three-dimensional calculation of tumor volume (in this case 1496 mm3).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the right-hand figure, a small cluster of individual cells (see inset) have disseminated far away from the implantation site and have become embedded in the dorsal skin.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By 4 weeks, a significant increase in the size and distribution of this GFP-labeled population can be easily visualized and is now largely confined to the anatomical area of the kidney of the fish (Figure 3B, right).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Real-time microscopy of cardiac contraction in the casper mutant. Distinct phases of systole and diastole can be examined by light microscopy.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While wild-type fish (Figure 2B, arrow) show a substantial layer of these reflective cells, the casper mutant has a complete absence of this layer, while the remaining skin structures are relatively intact, including epidermal scales and dermal collagen fibers as demonstrated by Masson's trichrome stain (data not shown).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Between 5 and 28 days posttransplant, 9/24 (37.5%) of all transplant recipients had evidence of distant metastasis, with the peak of initial dissemination occurring between 5 and 10 days.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The development of a robust, fertile, and easily maintained transparent adult zebrafish provides an important adult complement to the studies that are achievable in the transparent zebrafish embryo.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ability to calculate 3D tumor volume and whole body distribution of tumor cells provides an important quantitative analysis of engraftment after small numbers of tumor cells and offers the potential for monitoring in vivo effects of therapeutically useful molecules.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because nonmelanized but fluorescently labeled tumor cells can be visualized in the same manner, this tumor transplant model should be amenable to virtually any transplantable tumor.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that the transparent casper mutant allows for ready visualization of hematopoietic progenitor engraftment after a sublethal dose of 25 Gy, consistent with short-term hematopoietic engraftment.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Prior work from our laboratory has demonstrated that the transplantable hematopoietic stem/progenitor (HSPC) marrow population resides within the adult kidney, and can be isolated using flow cytometric analysis of forward and side scatter”
What the sources say
- Not checked — no full text of the sourcecites Traver et al., 2003 source
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data suggests that the casper fish will serve as a useful platform for researchers interested in processes such as stem cell engraftment and homing.”
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the scatter profile, multilineage engraftment has occurred, which indicates that the engrafted cells represent a primitive hematopoietic population.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“One limitation of this line is that it requires that both mutations (nacre and roy) be present in the homozygous state, which will require at least two breeding cycles to take advantage of currently available transgenic lines.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although similar to the “see through” medaka strain (Wakamatsu et al., 2001”
What the sources say
- Not checked — no full text of the sourcecites Wakamatsu et al., 2001 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, imaging of very deep tissues may require multiphoton microscopy, which is currently experimental in the zebrafish system.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because the adult zebrafish is well suited to genetic and small molecule based screens, the casper fish will allow for detailed in vivo study of stem and cancer biology in a vertebrate organism with great relevance to human biology.”
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The adult zebrafish is well suited to genetic and small molecule based screens.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, because the mutation in roy is currently unknown (but under active investigation), it is possible that this gene defect may affect some unknown aspects of tumor or stem cell biology, although it clearly does not affect survival.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“PET imaging, which can detect relatively small numbers of tumor cells, requires radioactive labeling of cell populations, is only moderately sensitive, and necessitates small animal PET scanners, which are not broadly available (Beckmann et al., 2007; Tai et al., 2005”
What the sources say
- Not checked — no full text of the sourcecites Beckmann et al., 2007 source
- Not checked — no full text of the sourcecites Tai et al., 2005
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although bioluminescence had high sensitivity in this study, it had limited spatial resolution (on the order of 1–10 mm), required several minutes of imaging per animal, showed detection of light from deep tissues is limited, and requires intravenous administration of substrate.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Analysis of adult zebrafish has been limited to embryogenesis due to the opacity of the adult fish.
“The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish.”
The paper relies on this without support.
The in vivo spatial resolution of the adult animal is limited due to the normal opacification of skin and subdermal structures.
“As in murine and human systems, however, the in vivo spatial resolution of the adult animal is limited due to the normal opacification of skin and subdermal structures.”
The paper relies on this without support.
Current in vivo imaging techniques such as bioluminescence, PET, CT, or MRI each have specific disadvantages in terms of resolution, sensitivity, or the need for costly equipment.
“Current in vivo imaging techniques, such as bioluminescence, PET, CT, or MRI, each have specific disadvantages in terms of resolution, sensitivity, or the need for costly equipment.”
The paper relies on this without support.
The in vivo behavior of stem cell populations is considerably more complex than in vitro models can offer.
“Because the in vivo behavior of stem cell populations is considerably more complex than in vitro models can offer, we now describe a transparent adult zebrafish model”
The paper relies on this without support.
Fluorescent imaging, though widely available and standard for gene function analysis in zebrafish embryos, is of limited use in adult wild-type zebrafish.
“Fluorescent imaging is widely available and is a standard method of analysis of gene function in zebrafish embryos; image acquisition is rapid, but is of limited use in adult wild-type zebrafish.”
The paper relies on this without support.
The adult zebrafish is well suited to genetic and small molecule based screens.
“Because the adult zebrafish is well suited to genetic and small molecule based screens”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“To date none of these strategies produce normally behaving larvae that are transparent in both the body and the eyes.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The combinatorial crystal mutant (albb4/b4;nacrew2/w2;roya9/a9) was generated by sequentially crossbreeding three different single mutant strains, namely nacrew2/w2 (ref. 9), roya9/a9 (ref. 4) and albb4/b4 (ref. 18) mutants.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The casper mutant was obtained by crossing nacrew2/w2 and roya9/a9 mutants, as previously described4.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Compared to the previously described combinatorial pigmentation mutant casper that has pigmented eyes4, the crystal mutant constitutes a significant improvement for in vivo imaging of tissues inside or between the eyes.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Common strategies to reduce zebrafish skin pigmentation can be grouped in two categories: 1) use of chemical compounds interfering with the synthesis of melanin, the most popular one being 1-phenyl-2-thiourea (PTU)8; 2) use of pigmentation mutants in which genes controlling either pigment formation, chromatophore formation or interactions between chromatophores have been inactivated469.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“This strategy has been previously implemented to generate the double mutant casper, which lacks all melanophores and iridophores4.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Compared to the previously described double mutant casper (nacrew2/w2;roya9/a9)4, where internal organs are also visible, the triple mutant crystal (nacrew2/w2;albb4/b4;roya9/a9) lacks melanin in the RPE (Fig. 1b).”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“More specifically, compared to casper mutants4, crystal fish are superior in terms of optical transparency when imaging inside or between the eyes.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Overall, the crystal mutant constitutes a significant improvement in the optical accessibility of both larval and adult zebrafish, even superior to the previously described combinatorial mutant casper4, which is characterised by black-pigmented eyes.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“The roy orbison (roya9/a9) mutant shows a complete lack of iridophores4.”
From A crystal-clear zebrafish for in vivo imaging (2016) · cites this paper as [4]
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Metadata
- Authors
- White, R. M., Sessa, A., Burke, C., Bowman, T., LeBlanc, J., Ceol, C., Bourque, C., Dovey, M., Goessling, W., Burns, C. E., & Zon, L. I.
- Affiliations
- Boston Children's Hospital (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Zon, Leonard I.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 2
- Issue
- 2
- Pages
- 183-189
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2292119
- OpenAlex
- W2019751519
- Cited by
- 1,408
- References
- 35
- Citations by year
- 2026: 71 · 2025: 96 · 2024: 90 · 2023: 91 · 2022: 126 · 2021: 106 · 2020: 103 · 2019: 93 · 2018: 81 · 2017: 89 · 2016: 99 · 2015: 59 · 2014: 73 · 2013: 54 · 2012: 52
- FWCI
- 17.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1993 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- American Society of Clinical Oncology
- National Institutes of Health
- National Cancer Institute (R01CA103846)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053298)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- hematopoietic stem and progenitor cells, engraftment, metastasis, cancer stem cells, transgenic zebrafish
- MeSH terms
- Albinism, Animals, Flow Cytometry, Light, Neoplasm Transplantation, Pigmentation, Stem Cells, Zebrafish, Models, Animal, Stem Cell Transplantation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-02, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-02 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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