Analysis Tools
cellular
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• cultured fibroblasts exhibit a 2-fold increase in oxidative stress compared to wild-type cells
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Allele Symbol Allele Name Allele ID |
Nfe2l1tm1Ywk targeted mutation 1, Yuet Wai Kan MGI:2385929 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cultured fibroblasts exhibit a 2-fold increase in oxidative stress compared to wild-type cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• homozygotes are recovered at an increasingly reduced Mendelian frequency after E12.5
• although a significant number of viable homozygotes is still present at E16.5, only a few homozygotes are identified by E17.5-E18.5
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• on very rare occasions, live homozygotes are identified immediately after birth; however, these appear significantly pale and die within a few hours of birth
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• homozygotes display a non-cell autonomous defect in fetal liver erythropoiesis due to a delay or arrest of erythroid cell maturation
• at E15.5-E16.5, mutant livers display only a few erythroid cells beyond the normoblast stage; only a few normoblasts, reticulocytes, and mature enucleated RBCs are observed within the vessels and sinusoids
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• homozygotes are anemic as a result of abnormal fetal liver hematopoiesis
• however, no defect in globin gene expression or other major developmental abnormalities are observed
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• by E16.5, the hematocrits of mutant embryos are reduced by ~50% relative to those of control embryos
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• at E16.5, peripheral blood smears of mutant embryos exhibit a high % of nucleated RBCs (20%) relative to wild-type and heterozygous embryos (<1%), inidcating persistence of yolk-sac derived primitive erythrocytes
• while a comparable number of nucleated RBCs is noted at E13.5, the number of definitive enucleared RBCs is decreased in mutant embryos relative to controls
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• at E10.5-E12.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos
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• at E12.5, mutant livers are visibly smaller than wild-type livers
• a prominent reduction in liver size is evident by E13.5-E14.5
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• at E15.5, mutant livers are pale
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• at E10.5-E12.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos
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• by E13.5-E15.5, mutant embryos are pale relative to wild-type or heterozygous embryos
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice
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• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice
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• at 4 weeks
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• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver
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• note: apoptotic cells and necrosis are seen in 4 weeks old mutant mice liver
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• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver
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• at 4 weeks, fatty vacuolated cells in liver had a 3-fold elevation in triglyceride levels
• lipid accumulation was also seen in cultures of primary hepatocytes derived from mutant mice
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• pericentral and pericellular fibrosis was seen in older animals
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• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice
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• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice
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• note: apoptotic cells and necrosis are seen in 4 weeks old mutant mice liver
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:97188 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Abnormal development of Nfe2l1tm1Ywk/Nfe2l1tm1Ywk Nfe2l2tm1Ywk/Nfe2l2tm1Ywk embryos with increased apoptosis
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• mice die between E11.5 and E13.5
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• fibroblasts exhibit increased cell death in 21% oxygen conditions unlike wild-type cells
• however, treatment of cells with vitamin E or N-acetylcysteine decreases cell death due to oxidative stress
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• at E10.5, embryos exhibit increased apoptosis in the brain, branchial arches, lung, and gut compared to wild-type mice
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• primary fibroblasts exhibit a 10-fold higher rate of apoptosis compared to wild-type cells
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• cultured fibroblasts exhibit a 4-fold increase in oxidative stress compared to wild-type cells
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• E10.5 mutants are developmentally delayed
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• small at E10.5
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• E10.5 mutants are developmentally delayed
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• small at E10.5
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/16/2024 MGI 6.23 |
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