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Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice
Open accessAbstract
The functional redundancy of the three mammalian Golgi-localized, γ-ear–containing, ADP-ribosylation factor-binding proteins (GGAs) was addressed in a previous study. Using insertional mutagenesis, we found that Gga1 or Gga3 homozygous knockout mice were for the most part normal, whereas mice homozygous for two different Gga2 gene-trap alleles exhibited either embryonic or neonatal lethality in the C57BL/6 background, depending on the source of the vector utilized (Byg vs. Tigm, respectively). We now show that the Byg strain harbors a disrupted Gga2 allele that is hypomorphic, indicating that the Byg lethality is attributable to a mechanism independent of GGA2. This is in contrast to the Tigm Gga2 allele, which is a true knockout and establishes a role for GGA2 during the neonatal period. Placement of the Tigm Gga2 allele into the C57BL6/Ola129Sv mixed background results in a lower incidence of neonatal lethality, showing the importance of genetic background in determining the requirement for GGA2 during this period. The Gga2−/− mice that survive have reduced body weight at birth and this runted phenotype is maintained through adulthood.
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Written from the paper’s full text.
TL;DR
The Byg Gga2 gene-trap allele is hypomorphic, so its embryonic lethality is not caused by loss of GGA2, whereas the Tigm Gga2 allele is a true knockout that causes neonatal lethality whose severity depends on genetic background. Surviving Gga2−/− mice are runted from birth through adulthood.
Key findings
- Byg/Tigm compound heterozygous mice, which are Gga2−/− at the DNA level, were viable and normal, and GGA2 protein was detectable in them, showing the Byg allele is hypomorphic; Byg Gga2−/− embryonic lethality therefore has an unidentified cause independent of GGA2.
- In the C57BL/6NJ background, Tigm Gga2−/− mice showed >95% neonatal lethality; in an additional 65 offspring, only one Gga2−/− mouse survived beyond 2 wk.
- In the C57BL6/Ola129Sv mixed background, 14 of 25 Gga2−/− pups (56%) died within the first week, almost all within 48 hr, compared with 6% of wild-type and 10% of Gga2+/− mice; the difference was highly significant by Fisher exact test (P < 0.0001).
- Surviving Gga2−/− mice had reduced body weight at birth that persisted through adulthood; serum IGF-II levels were similar across genotypes, and brain CI-MPR, SorLA, and Sortilin levels were unaltered.
Methods
- Mouse genetics: Byg and Tigm Gga2+/− gene-trap mice in C57BL/6J and C57BL/6NJ backgrounds were crossed to generate Byg/Tigm compound heterozygotes; the Tigm allele was introduced into the C57BL6/Ola129Sv mixed background. Genotyping used PCR, and GGA2 expression was assessed by Western blotting of brain, heart, and lung extracts.
- Phenotyping: progeny were genotyped at birth and/or 1 wk, including dead pups; body weights were recorded from week 1 to week 12. Serum IGF-II was measured by ELISA (n = 16 per group), and brain CI-MPR, SorLA, and Sortilin were analyzed by Western blot.
- Statistics: Fisher exact test was used for mortality comparisons, and Student t test for IGF-II receptor data; weight comparisons used reported P values.
Limitations
- Stated: statistical analysis was not performed for female weight curves because of small sample size; the increased mortality of Gga2−/− mice at birth in the mixed background was not statistically significant based on sample size; the factor causing Byg Gga2−/− embryonic lethality remains unidentified.
- Evident: the Byg strain was not pursued further after being shown hypomorphic, and the mechanism by which the mixed genetic background partially rescues Tigm Gga2−/− neonatal lethality is not identified; the cause of the runted phenotype remains unknown beyond exclusion of circulating IGF-II and major changes in CI-MPR, SorLA, or Sortilin turnover.
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- Findingown data
Placement of the Tigm Gga2 allele into the C57BL6/Ola129Sv mixed background results in a lower incidence of neonatal lethality than in the C57BL/6NJ background.
“Placement of the Tigm Gga2 allele into the C57BL6/Ola129Sv mixed background results in a lower incidence of neonatal lethality, showing the importance of genetic background in determining the requirement for GGA2 during this period.”
- Also stated in: § Discussion · plain
“with more than 95% lethality occurring in the C57BL/6NJ background (Govero et al. 2012) compared with 56% in the C57BL6/Ola129Sv mixed genetic background.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Also stated in: § Discussion · plain
- Findingown data
Progeny of every possible genotype were obtained from the crosses, except Byg Gga2−/− (Byg/Byg) mice.
“Importantly, progeny corresponding to every possible genotype were obtained from the crosses shown in Figure 1, A–C, with the exception of Byg Gga2−/− mice (Byg/Byg) (Figure 1B)”
Quote in the paperSubstantial claim - Findingown data
Tigm Gga2−/− mice occasionally express very low levels of GGA2, in the range of 1-2.5% relative to wild-type.
“Long exposure of the GGA2 blots also revealed that an occasional Tigm Gga2−/− pup expresses very low levels of GGA2 that could at times be detected (Figure S2, long exposure of brain and lung GGA2) but, for the most part, even if there was low level expression, it was below the detection limit”
- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · hedged
“Western blot analysis of varying amounts of wt brain lysate run alongside a Gga2−/− brain lysate where some expression was observed, indicating that this low level expression is in the range of 1–2.5% relative to wt”
Quote in the paperNot a substantial claim - Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · hedged
- Findingown data
The embryonic lethality associated with the Byg allele in the homozygous state persists in the C57BL/6NJ background.
“highlighting the fact that the embryonic lethality associated with the Byg allele in the homozygous state persists in the C57BL/6NJ background.”
Quote in the paperSubstantial claim - Findingcitation
Tigm Gga2−/− mice in the C57BL/6NJ background display a neonatal lethal phenotype with more than 95% mortality.
“We previously presented data showing that the Tigm Gga2−/− phenotype in the C57BL/6NJ background is neonatal lethal, exhibiting more than 95% mortality rate with one single survivor that lived beyond 3 wk (Govero et al. 2012).”
- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · boosted
“These results confirm our previous finding that Gga2−/− mice display a neonatal lethal phenotype in the C57BL/6NJ background.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · boosted
- Findingown data
Byg Gga2+/− mice frequently express GGA2 protein at levels similar to wild-type.
“the het mice frequently expressed GGA2 protein at a level similar to wt”
- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
“Strikingly, in this litter the two Byg Gga2+/− pups (Figure 1D +/Byg, lanes 7 and 8) had higher brain expression of GGA2 than the Tigm Gga2+/− pup (+/Tigm, lane 5) similar to wt (compare lane 3 with lanes 7 and 8).”
Quote in the paperSubstantial claim - Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
- Findingown data
Serum IGF-II levels of day 1 pups are similar in all three genotypes.
“The levels were similar in all three genotypes, indicating that lack of circulating IGF-II is not the cause of the reduced body weight of Gga2−/− mice (Figure 4A).”
Quote in the paperSubstantial claim - Findingown data
In the mixed background, Gga2−/− mice have no detectable GGA2 protein in brain in most instances.
“Western blot analysis of brain tissue extracts prepared from day 1 pups in the mixed background probed for GGA2 showed no detectable protein in the Gga2−/− mice in most instances (representative pups shown in Figure 2C), although occasionally the same low-level expression was observed as with the Tigm Gga2−/− mice in the C57BL/6NJ background.”
Quote in the paperSubstantial claim - Findingown data
Plasma levels of four different lysosomal acid hydrolases are similar between wt and Gga2−/− mice.
“Moreover, plasma levels of four different lysosomal acid hydrolases were assayed and found to be similar between wt and Gga2−/− mice (not shown)”
Quote in the paperSubstantial claim - Findingcitation
Histological examination did not reveal any pathologic changes in the internal organs of the surviving Gga2−/− mouse.
“Histological examination did not reveal any pathologic changes in the internal organs (not shown), similar to the situation with the newborn Gga2 knockouts (Govero et al. 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Findingcitation
The lethality rate in the C57BL/6NJ background is more than 95% in the Gga2−/− homozygous state.
“The result is also significantly different from the finding in the C57BL/6NJ background, where the lethality rate is more than 95% in the Gga2−/− homozygous state (Govero et al. 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Findingreasoning
Compound heterozygous Byg/Tigm mice that are Gga2−/− at the DNA level are viable and normal.
“As expected if the Byg allele is hypomorphic, all the compound hets that were born were viable and normal in all respects even though these mice are Gga2−/− at the DNA level.”
Quote in the paperSubstantial claim - Findingown data
Expression levels of CI-MPR, SorLA, and Sortilin are unaltered in brain tissue of Gga2−/− mice.
“We also found that the expression level of the CI-MPR, SorLA, and Sortilin are unaltered in brain tissue of Gga2−/− mice (Figure 4B)”
Quote in the paperSubstantial claim - Findingown data
In the mixed genetic background, Gga2−/− mice are born in near accordance with the expected Mendelian ratio.
“Figure 2A shows that Gga2−/− mice in the mixed genetic background are born in near accordance with the expected Mendelian ratio, as was the case in the C57BL/6NJ background (Govero et al. 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Findingown data
In the mixed genetic background, 56% (14/25) of Gga2−/− offspring died within the first week, almost all within the first 48 hr.
“Of the 25 Gga2−/− offspring that were born within this group, 14 (56%) died within the first week, with almost all dying within the first 48 hr.”
Quote in the paperSubstantial claim - Interpretationown data
GGA2 is important for viability of neonates.
“establishes a role for GGA2 during the neonatal period.”
- Also stated in: § Discussion · hedged
“we conclude that GGA2 is important for viability of neonates but appears to be dispensable once the mice are past 3 wk of age.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Interpretationown data
The Byg Gga2 gene-trap allele is hypomorphic.
“We now show that the Byg strain harbors a disrupted Gga2 allele that is hypomorphic, indicating that the Byg lethality is attributable to a mechanism independent of GGA2.”
- Also stated in: § Abstract · hedged
“indicating that the Byg Gga2 gene-trap allele is likely to be a hypomorphic allele.”
- Also stated in: § Discussion · boosted
“The current experiments unequivocally demonstrate that the early embryonic lethality of the Byg Gga2−/− mice is not due the absence of GGA2 because the Byg Gga2 gene-trap allele is clearly hypomorphic.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · hedged
- Interpretationown data
The Tigm Gga2 allele is a true knockout.
“This is in contrast to the Tigm Gga2 allele, which is a true knockout and establishes a role for GGA2 during the neonatal period.”
- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
“Immunoblot analysis of brain tissue extracts (Figure 1E) showed that the Tigm Gga2−/− pup in this litter (Tigm/Tigm, lane 2) had no detectable GGA2, even on long exposure of the blot”
Quote in the paperSubstantial claim - Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
- Interpretationown data
GGA2 appears dispensable once mice are past 3 wk of age.
“we conclude that GGA2 is important for viability of neonates but appears to be dispensable once the mice are past 3 wk of age.”
- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · plain
“Of the surviving Tigm Gga2−/− mice in the C57BL6/Ola129Sv mixed background, none have died beyond the 3-wk period, with the oldest mouse now 9 months old, and both males and females are fertile.”
Quote in the paperSubstantial claim - Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · plain
- Interpretationreasoning
The embryonic lethality associated with the Byg Gga2 gene-trap allele is not attributable to loss of GGA2.
“indicating that the Byg lethality is attributable to a mechanism independent of GGA2.”
- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · boosted
“These results confirm that the embryonic lethality of the Byg Gga2−/− mice is not attributable to the absence of GGA2.”
- Also stated in: § Discussion · boosted
“The current experiments unequivocally demonstrate that the early embryonic lethality of the Byg Gga2−/− mice is not due the absence of GGA2 because the Byg Gga2 gene-trap allele is clearly hypomorphic.”
Quote in the paperSubstantial claim - Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · boosted
- Premisecitation
GGA2 expression in brain is highest at embryonic day 9 through the end of week 1, then declines substantially reaching the lowest level in the adult mouse brain.
“We have shown that even though brain expression of the three GGAs was detected at all stages of development, GGA2 expression was highest at embryonic day 9 (day E9) through the end of week 1, and then declined substantially reaching the lowest level in the adult mouse brain (Govero et al. 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Premisecitation
Brain expression levels of GGA1 and GGA3 remain consistently high from day E9 through the adult stage.
“Brain expression levels of GGA1 and GGA3, however, remained consistently high from day E9 through the adult stage (Govero et al. 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Govero et al. 2012 source
- Interpretationown data
Genetic background is important in determining viability in the absence or near-complete loss of GGA2.
“showing the importance of genetic background in determining the requirement for GGA2 during this period.”
- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · hedged
“Taken together, these results indicate that the partial rescue of the neonatal lethality in the mixed background is not due to increased expression of GGA2, but rather it is the genetic background of the mice that plays an important role in determining viability in the absence or near-complete loss of GGA2.”
- Also stated in: § Discussion · boosted
“In this regard, the genetic background has a major impact in terms of the tolerance to the loss of GGA2”
Quote in the paperSubstantial claim - Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · hedged
- Interpretationown data
The Byg Gga2 gene-trap allele's alternate splicing around the gene-trap cassette in many instances gives rise to near-normal levels of GGA2.
“In the case of the Byg Gga2 gene-trap allele, this alternate splicing around the gene-trap cassette in many instances gives rise to near-normal levels of GGA2”
Quote in the paperSubstantial claim - Interpretationreasoning
These findings are in concordance with some non-redundant and vital function(s) mediated by GGA2 early in the life of a mouse.
“These findings are in concordance with some non-redundant and vital function(s) mediated by GGA2 early in the life of a mouse.”
Quote in the paperSubstantial claim - Interpretationown data
The Byg allele produces wild-type message in addition to the chimeric Gga2-βgal transcript.
“indicating that the Byg allele must be producing wt message in addition to the chimeric Gga2-βgal transcript.”
Quote in the paperSubstantial claim - Interpretationown data
The partial rescue of neonatal lethality in the mixed background is not due to increased expression of GGA2.
“Taken together, these results indicate that the partial rescue of the neonatal lethality in the mixed background is not due to increased expression of GGA2”
- Also stated in: § Discussion · plain
“This difference is not due to increased expression of GGA2 in the mixed background.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Interpretationown data
Acid hydrolase sorting is normal in the absence of GGA2.
“indicating that acid hydrolase sorting is normal in the absence of GGA2.”
Quote in the paperSubstantial claim - Premisecitation
GGA1/GGA3 double knockout mice show 58% neonatal lethality in the mixed genetic background.
“Our previous study demonstrated that GGA1/GGA3 double knockout mice show 58% neonatal lethality in the mixed genetic background, similar to the 56% lethality due to loss of GGA2 in the same background.”
Quote in the paperSubstantial claim - Interpretationreasoning
The early embryonic lethality of Byg Gga2−/− mice is the consequence of another factor that has yet to be identified.
“showing that the early embryonic lethality is the consequence of another factor that has yet to be identified.”
Quote in the paperSubstantial claim - Interpretationown data
Major differences in the turnover of CI-MPR, SorLA, and Sortilin are excluded in the absence of GGA2.
“excluding major differences in the turnover of these receptors in the absence of GGA2.”
Quote in the paperSubstantial claim - Interpretationown data
Lack of circulating IGF-II is not the cause of the reduced body weight of Gga2−/− mice.
“indicating that lack of circulating IGF-II is not the cause of the reduced body weight of Gga2−/− mice”
Quote in the paperSubstantial claim
- It may state two separate claims as one. 9
- Probably not a substantial claim. 2
It may state two separate claims as one.
Findingown dataThe Gga2−/− mice that survive have reduced body weight at birth and this runted phenotype is maintained through adulthood.
“The Gga2−/− mice that survive have reduced body weight at birth and this runted phenotype is maintained through adulthood.”
- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · plain
“One consistent phenotype that was observed with the Gga2−/− mice in the mixed genetic background was that both males and females were significantly smaller than their siblings”
- Also stated in: § Abstract · boosted
“These studies show that the Gga2−/− mice have a runted phenotype.”
Quote in the paperSubstantial claim- Also stated in: § Influence of genetic background on neonatal lethality of Tigm Gga2−/− gene-trap mice · plain
It may state two separate claims as one.
Findingown dataThe mortality rate of wt and Gga2+/− mice in the mixed background is 6% and 10%, respectively.
“This is in stark contrast to the mortality rate of wt and Gga2+/− mice in the same background (6% and 10%, respectively).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataThe six deaths at birth of Gga2−/− mice were not significant compared to the two wt deaths at birth, whereas the 14 deaths neonatally were highly significant by Fisher exact test (P < 0.0001).
“The six deaths at birth of the Gga2−/− mice were not significant compared to the two wt deaths at birth, whereas the 14 deaths (*) that occurred neonatally were highly significant, as determined by the Fisher exact test (P < 0.0001).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataLoss of GGA1 or GGA3 is well-tolerated in both C57BL/6J and mixed genetic backgrounds.
“We have now backcrossed Gga3−/− mice into the C57BL/6J background as well and have found no obvious difference between the two genetic backgrounds with either knockout strain, indicating that loss of GGA1 or GGA3 is well-tolerated in both strains, in contrast to the loss of GGA2.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn the mixed genetic background, Gga2−/− mice exhibit increased mortality compared to wt and hets at birth, but the difference was not statistically significant based on sample size.
“Of note, the Gga2−/− mice exhibited increased mortality compared to wt and hets at this time point, although the difference was not statistically significant based on our sample size.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataAn additional surviving Gga2−/− male weighed 50% less than its littermates and was killed at 3 wk due to marked cachexia.
“This surviving mouse was a male that weighed 50% less than its littermates and had to be killed at 3 wk due to marked cachexia.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSurviving Tigm Gga2−/− mice in the mixed background have no deaths beyond 3 wk, the oldest is 9 months old, and both males and females are fertile.
“Of the surviving Tigm Gga2−/− mice in the C57BL6/Ola129Sv mixed background, none have died beyond the 3-wk period, with the oldest mouse now 9 months old, and both males and females are fertile.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataGGA2 is detected in every Byg/Tigm compound het, with substantial variability in expression level.
“Of note, GGA2 was detected in every compound het (Byg/Tigm, lanes 1, 3, 4, 5, 7, and 8), although there was substantial variability in the expression level (compare lanes 4 and 5 to 7 and 8.).”
- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
“Analysis of brain, heart, and lung tissue extracts from other litters also showed variation in the expression of GGA2 among the compound hets and Byg Gga2+/− (+/Byg) pups”
Quote in the paperSubstantial claim- Also stated in: § Generation and analysis of Gga2−/− compound heterozygotes · plain
It may state two separate claims as one.
Findingown dataThe surviving Gga2−/− mouse in the C57BL/6NJ background was a female that was 25% smaller than its littermates at 4 wk of age but had a normal lifespan.
“The surviving Gga2−/− mouse was a female that was 25% smaller than its littermates at 4 wk of age but had a normal lifespan.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductnone givenThe Byg strain was backcrossed for at least eight generations into the C57BL/6 genetic background before being crossed with the Tigm strain.
“The Byg strain was backcrossed for at least eight generations into the C57BL/6 genetic background before being crossed with the Tigm strain, also in the C57BL/6 background.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown dataStatistical analysis was not performed with the females due to the small sample size.
“Statistical analysis was not performed with the females due to the small sample size.”
Quote in the paperNot a substantial claim
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Isobe, M., Lee, S., Waguri, S., & Kametaka, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0207533 · Cited by 13
Sun, F., Zhang, R., Li, T., Zhang, L., Chen, X., Liang, Y., Chen, L., Zou, S., & Dong, H. (2022) · Environmental Microbiology · doi:10.1111/1462-2920.16279 · Cited by 5
Adaptor Proteins: Inter-Organelle Traffic Controllers
Madhivanan, K., Hsieh, W.-C., Pearson, M., & Aguilar, R. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00072-9
GGAs : Regulation of Multiple Sorting Pathways and Potential Association With Human Diseases
Wang, Q., Mei, J., Li, S., Zhang, G., Qiu, J., & Li, X. (2026) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.71215
Metadata
- Authors
- Doray, B., Govero, J., & Kornfeld, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Kornfeld, Stuart
- Venue
- G3 Genes|Genomes|Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-01
- Volume
- 4
- Issue
- 5
- Pages
- 885-890
- ISSN
- 2160-1836 (ISSN-L)
- PMC
- PMC4025487
- OpenAlex
- W2110211353
- Semantic Scholar
- 06a2fc0bf83404a4875bda779bcd84141a68f5cd
- Cited by
- 9
- References
- 22
- Citations by year
- 2026: 1 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 0.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- G3 Genes Genomes Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P50AG005681)
- National Cancer Institute (R37CA008759, CA-008759-44)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020579)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- GGA2, gene trap mice, neonatal lethality, genetic background, functional redundancy, hypomorphic allele, knockout alleles, C57BL/6 mice, insertional mutagenesis
- MeSH terms
- Alleles, Animals, Female, Genes, Lethal, Genotype, Male, Phenotype, Mice, Knockout, Adaptor Proteins, Vesicular Transport, Mice
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 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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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