Phenotypes associated with this allele

• Allele Symbol: Nfe2l1^tm1Ywk
• Allele Name: targeted mutation 1, Yuet Wai Kan
• Allele ID: MGI:2385929
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk	involves: 129X1/SvJ	MGI:3839458
hm2	Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk	involves: 129X1/SvJ * C57BL/6J	MGI:2672111
cn3	Nfe2l1^tm1Jefc/Nfe2l1^tm1Ywk Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129X1/SvJ * C57BL/6J	MGI:3575312
cx4	Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk Nfe2l2^tm1Ywk/Nfe2l2^tm1Ywk	involves: 129X1/SvJ	MGI:3839459

Genotype
MGI:3839458

hm1

• Allelic Composition: Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk
• Genetic Background: involves: 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

oxidative stress ( J:86725 )

• cultured fibroblasts exhibit a 2-fold increase in oxidative stress compared to wild-type cells

Genotype
MGI:2672111

hm2

• Allelic Composition: Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

neonatal lethality, complete penetrance ( J:46990 )

• on very rare occasions, live homozygotes are identified immediately after birth; however, these appear significantly pale and die within a few hours of birth

lethality throughout fetal growth and development, incomplete penetrance ( J:46990 )

• 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

hematopoietic system

abnormal erythropoiesis ( J:46990 )

• 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

anemia ( J:46990 )

• 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

decreased hematocrit ( J:46990 )

• by E16.5, the hematocrits of mutant embryos are reduced by ~50% relative to those of control embryos

increased nucleated erythrocyte cell number ( J:46990 )

• 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

growth/size/body

embryonic growth retardation ( J:46990 )

decreased embryo size ( J:46990 )

• at E10.5-E12.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos

liver/biliary system

small liver ( J:46990 )

• 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

pale liver ( J:46990 )

• at E15.5, mutant livers are pale

embryo

embryonic growth retardation ( J:46990 )

decreased embryo size ( J:46990 )

• at E10.5-E12.5, mutant embryos are significantly smaller than wild-type or heterozygous embryos

integument

pallor ( J:46990 )

• by E13.5-E15.5, mutant embryos are pale relative to wild-type or heterozygous embryos

Genotype
MGI:3575312

cn3

• Allelic Composition: Nfe2l1^tm1Jefc/Nfe2l1^tm1Ywk; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

neoplasm

increased hepatocellular carcinoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

increased liver adenoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

homeostasis/metabolism

increased circulating alanine transaminase level ( J:97188 )

• at 4 weeks

immune system

liver inflammation ( J:97188 )

• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver

liver/biliary system

liver inflammation ( J:97188 )

• infiltration of inflammatory cells are seen in 4 weeks old mutant mice liver

hepatic necrosis ( J:97188 )

• note: apoptotic cells and necrosis are seen in 4 weeks old mutant mice liver

hepatic steatosis ( J:97188 )

• 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

increased hepatocellular carcinoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

increased liver adenoma incidence ( J:97188 )

• at 10-12 months, enlarged livers with multiple tumors were seen in 100% (12/12) mutant mice

liver fibrosis ( J:97188 )

• pericentral and pericellular fibrosis was seen in older animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:97188

Genotype
MGI:3839459

cx4

• Allelic Composition: Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk; Nfe2l2^tm1Ywk/Nfe2l2^tm1Ywk
• Genetic Background: involves: 129X1/SvJ

Abnormal development of Nfe2l1^tm1Ywk/Nfe2l1^tm1Ywk Nfe2l2^tm1Ywk/Nfe2l2^tm1Ywk embryos with increased apoptosis

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:86725 )

• mice die between E11.5 and E13.5

cellular

increased cellular sensitivity to oxidative stress ( J:86725 )

• 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

increased apoptosis ( J:86725 )

• at E10.5, embryos exhibit increased apoptosis in the brain, branchial arches, lung, and gut compared to wild-type mice

increased fibroblast apoptosis ( J:86725 )

• primary fibroblasts exhibit a 10-fold higher rate of apoptosis compared to wild-type cells

oxidative stress ( J:86725 )

• cultured fibroblasts exhibit a 4-fold increase in oxidative stress compared to wild-type cells

embryo

embryonic growth retardation ( J:86725 )

• E10.5 mutants are developmentally delayed

decreased embryo size ( J:86725 )

• small at E10.5

growth/size/body

embryonic growth retardation ( J:86725 )

• E10.5 mutants are developmentally delayed

decreased embryo size ( J:86725 )

• small at E10.5