Mouse Genome Informatics
hm
    Fancctm1Mgo/Fancctm1Mgo
involves: 129S4/SvJaeSor * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
reproductive system
• at 6-8 weeks of age, mutant ovaries are almost entirely devoid of follicles (J:61512)
• at 6-8 weeks of age, homozygotes exhibit very small ovaries (J:61512)
• at 6-8 weeks of age, homozygotes show significant ovarian cortical hypoplasia as well as hyperplasia of the interstitial cells (J:61512)
• at 2 months, male homozygotes display a mosaic pattern of seminiferous tubules devoid of germ cells and normal tubules (J:61512)
• abnormal tubules that are devoid of mature sperm contain only Sertoli cells (J:61512)
• at 4 weeks or later, male homozygotes exhibit significantly reduced testicular weights (J:61512)
• at 6-8 weeks of gae, homozygotes show endometrial atrophy with reduced stroma cellularity (J:61512)
• homozygous neonates of both sexes exhibit a developmental germ cell defect; however, germ cell depletion is more severe in females
• newborn mutant ovaries consist of granulosa cells and almost no germ cells (J:61512)
• newborn mutant testes contain significantly less germ cells (J:61512)
• female homozygotes display significantly impaired fertility (J:61512)
• breeding of 2-mo-old female homozygotes with heterozygous males resulted in either no litters at all or only one litter of 1-2 pups
• breeding of 4-mo-old female homozygotes with wild-type males generated only 6 pups in 4 pregnanies, with an average litter size of 1.5 pups, over a 3-mo period

endocrine/exocrine glands
• at 6-8 weeks of age, mutant ovaries are almost entirely devoid of follicles (J:61512)
• at 6-8 weeks of age, homozygotes exhibit very small ovaries (J:61512)
• at 6-8 weeks of age, homozygotes show significant ovarian cortical hypoplasia as well as hyperplasia of the interstitial cells (J:61512)
• at 2 months, male homozygotes display a mosaic pattern of seminiferous tubules devoid of germ cells and normal tubules (J:61512)
• abnormal tubules that are devoid of mature sperm contain only Sertoli cells (J:61512)
• at 4 weeks or later, male homozygotes exhibit significantly reduced testicular weights (J:61512)

hematopoietic system
• in vitro, bone marrow cultures established from 6-mo-old homozygotes display significantly reduced CFU-GM and BFU-E colony growth; however, no such differences are noted at 2-4 months
• both mutant clonal progenitors (CFU-GM and BFU-E) are hypersensitive to the mitotic inhibitory effects of IFN-gamma, independent of age
• however, no anemia or abnormal blood parameters are detected in homozygotes up to 9 months of age

cellular
• in response to mitomycin C, mutant primary splenocytes accumulate in the G2 phase of the cell cycle, indicating a delay in cell cycle transit
• mutant skin fibroblasts are hyper-responsive to the clastogenic effect of mitomycin C and DEB, exhibiting chromosome breakage and other cytogenetic abnormalities
• some mutant skin fibroblast lines even exhibit spontaneous chromosome breakage, without exposure to clastogens
• however, homozygotes appear to remain tumor-free up to one year of age

Mouse Models of Human Disease
OMIM IDRef(s)
Fanconi Anemia, Complementation Group C; FANCC 227645 J:61512