Phenotypes Associated with This Genotype

Genotype
MGI:6281646

• Allelic Composition: Fan1^{tm1a(KOMP)Wtsi}/Fan1^{tm1a(KOMP)Wtsi}
• Genetic Background: 129S1.B6-Fan1^{tm1a(KOMP)Wtsi}
• Cell Lines: EPD0736_4_C08

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

cellular

increased sensitivity to induced cell death ( J:242198 )

• mouse embryonic fibroblasts (MEFs) treated with the genotoxins MMC or diepoxybutane show reduced colony formation ability and reduced survival compared to wild-type control MEFs

increased kidney cell proliferation ( J:242198 )

• cisplatin treated mutant kidneys show a greater increase in cell proliferation than wild-type kidneys and the Ki67+ nuclei are enlarged

growth/size/body

cachexia ( J:242198 )

• mice treated with cisplatin are severely dehydrated and cachectic, losing 30% of body weight compared to 10% body weight loss in wild-type mice and no mortality

• mice treated with a lower 2 mg/kg dose of cisplatin show reduced body weight by the third week and by 5 weeks are moribund compared to wild-type mice which appear healthy

homeostasis/metabolism

increased blood urea nitrogen level ( J:242198 )

• BUN levels are increased 9-fold over wild-type mice after treatment for 5 weeks with cisplatin

dehydration ( J:242198 )

• mice treated with cisplatin are severely dehydrated compared to treated wild-type mice

increased susceptibility to xenobiotic induced morbidity/mortality ( J:242198 )

• mice treated with 20 mg/kg of cisplatin show 100% mortality by post-injection day 7, with some dying already on day 2

increased physiological sensitivity to xenobiotic ( J:242198 )

• mice exhibit increased susceptibility to cisplatin toxicity in the kidney compared to wild-type mice, failing to recover from cisplatin-induced acute kidney injury 7 days post-treatment as in controls

immune system

tubulointerstitial nephritis ( J:242198 )

• mice treated with cisplatin show features of karyomegalic interstitial nephritis, with formation of karyomegalic nuclei in the proximal tubule, presence of interstitial infiltrate, loss of brush borders, and tubular dilation, segmental thickening of the tubular basement membrane and frequent thickening of the Bowmans capsule

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:242198 )

• mice treated with 20 mg/kg of cisplatin show 100% mortality by post-injection day 7, with some dying already on day 2

renal/urinary system

renal/urinary system phenotype ( J:242198 )

N • mice exhibit normal kidneys up to 18 months of age under normal conditions

increased kidney cell proliferation ( J:242198 )

• cisplatin treated mutant kidneys show a greater increase in cell proliferation than wild-type kidneys and the Ki67+ nuclei are enlarged

tubulointerstitial nephritis ( J:242198 )

• mice treated with cisplatin show features of karyomegalic interstitial nephritis, with formation of karyomegalic nuclei in the proximal tubule, presence of interstitial infiltrate, loss of brush borders, and tubular dilation, segmental thickening of the tubular basement membrane and frequent thickening of the Bowmans capsule

renal interstitial fibrosis ( J:242198 )

• cisplatin treated mutants show renal interstitial fibrosis which is not seen in treated wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
karyomegalic interstitial nephritis		DOID:0060911	OMIM:614817	J:242198