Phenotypes Associated with This Genotype

Genotype
MGI:5897864

• Allelic Composition: Fan1^{tm1d(KOMP)Wtsi}/Fan1^{tm1d(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N * FVB/N

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

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:232402 )

• following treatment with 10 mg/kg mitomycin C 90% of homozygotes die unlike similarly treated wild-type and heterozygous mice that tolerate this dose well

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:232402 )

• following treatment with 10 mg/kg mitomycin C 90% of homozygotes die unlike similarly treated wild-type and heterozygous mice that tolerate this dose well

increased physiological sensitivity to xenobiotic ( J:232402 )

• MEFs are hypersensitive to mitomycin C and also more sensitive to acetaldehyde and formaldehyde indicating a defect in interstrand cross-link repair

• mice treated with 10 mg/kg mitomycin C show increased weight loss and mortality following treatment

• mice treated with 10 mg/kg mitomycin C show depletion of hematopoietic progenitor cells by 7 days after treatment resulting in pronounced hypocellularity of the bone marrow, neutropenia and cytopenia

renal/urinary system

renal/urinary system phenotype ( J:232402 )

N • despite karyomegaly, no increases in the levels of blood urea nitrogen, creatinine, phosphorus, or magnesium are detected

abnormal renal tubule morphology ( J:232402 )

• karyomegaly is detectable at 6 months of age and increases with age

• proportion of cells with larger than median nuclear size increases more than twofold to 29% of cells by 12 months of age

• karyomegaly is seen in tubular cells but not glomeruli

liver/biliary system

increased hepatocyte karyomegaly ( J:232402 )

• at 18 months of age, a large fraction (>50%) of hepatocyte nuclei are significantly enlarged

decreased liver function ( J:232402 )

• indicated by increased alanine transaminase and aspartate transaminase levels with decreased albumin and globulin levels in older mice with karyomegalic hepatocytes

hematopoietic system

hematopoietic system phenotype ( J:232402 )

N • no signs of bone marrow dysfunction are detected at 3 or 18 months of age

abnormal hematopoietic stem cell physiology ( J:232402 )

• increased sensitivity to mitomycin C induced hematopoietic progenitor cell death

cellular

abnormal cell nucleus morphology ( J:232402 )

• karyomegaly in hepatocytes and renal tubular cells but not in the spleen in older mice

polyploidy ( J:232402 )

• kidney and liver cells with enlarged nuclei show signs of polyploidy

increased hepatocyte karyomegaly ( J:232402 )

• at 18 months of age, a large fraction (>50%) of hepatocyte nuclei are significantly enlarged

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
karyomegalic interstitial nephritis		DOID:0060911	OMIM:614817	J:232402