Phenotypes Associated with This Genotype

Genotype
MGI:5897798

• Allelic Composition: Fan1^tm1.1Jrou/Fan1^tm1.1Jrou
• Genetic Background: involves: 129P2/OlaHsd

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

renal/urinary system

renal/urinary system phenotype ( J:232403 )

N • unlike in human karyomegalic interstitial nephritis patients, mice do not show signs of major kidney dysfunction

abnormal renal tubule morphology ( J:232403 )

• a spectrum of tubular changes are seen (dilation, degeneration, atrophy, and increased infiltration of inflammatory cells in interstitial spaces) particularly in older mice

• thickened basement membranes are often seen in older mice

abnormal renal tubule epithelium morphology ( J:232403 )

• prominent karyomegaly that develops by 6 months of age and is more severe at 20 months of age

• increase in the population of cell nuclei with 4n or 8n DNA content

renal tubule atrophy ( J:232403 )

dilated renal tubule ( J:232403 )

homeostasis/metabolism

abnormal DNA repair ( J:232403 )

• MEFs are hypersensitive to DNA cross-link inducing genotoxins indicating a defect in interstrand cross-link repair

increased physiological sensitivity to xenobiotic ( J:232403 )

• MEFs are hypersensitive to DNA cross-link inducing genotoxins indicating a defect in interstrand cross-link repair

• pronounced G2 arrest and increase frequency of chromosomal abnormalities in MEFs after exposure to mitomycin C or diepoxybutane

cellular

polyploidy ( J:232403 )

• increase in the population of kidney cell nuclei with 4n or 8n DNA content

• induction of interstrand cross-links results in a modest but signifcant increase in the proportion of cells with 8n DNA content in primary MEFS from homozygous mice but not in cells from wild-type controls

abnormal DNA repair ( J:232403 )

• MEFs are hypersensitive to DNA cross-link inducing genotoxins indicating a defect in interstrand cross-link repair

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
karyomegalic interstitial nephritis		DOID:0060911	OMIM:614817	J:232403