Phenotypes Associated with This Genotype

Genotype
MGI:3618892

• Allelic Composition: Fanca^tm1Faw/Fanca^tm1Faw
• Genetic Background: involves: 129P2/OlaHsd * FVB

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

reproductive system

abnormal ovary morphology ( J:63742 )

♀ • mutant ovaries consist predominantly of interstitial cells

absent mature ovarian follicles ( J:63742 )

♀ • mutant ovaries contain few or almost no mature follicles

small seminiferous tubules ( J:63742 )

♂ • male homozygotes display atrophic seminiferous tubules with significantly reduced spermatogenesis; some tubuli mainly have Sertoli cells

increased Leydig cell number ( J:63742 )

♂ • mutant testes display diffuse hyperplasia of Leydig cells

abnormal spermatogenesis ( J:63742 )

♂ • mutant testes exhibit seminiferous tubules with normal spermatogenesis next to abnormal tubules with markedly reduced spermatogenesis

small gonad ( J:63742 )

• both male and female homozygotes exhibit hypogonadism

reduced female fertility ( J:63742 )

♀ • female homozygotes cease breeding between 10 and 21 weeks of age

decreased litter size ( J:63742 )

reduced male fertility ( J:63742 )

♂ • male homozygotes stop breeding after ~20 weeks of age, with the majority becoming completely infertile

♂ • occasionally, some males regain reproductivity after a non-reproductive period of several months

endocrine/exocrine glands

abnormal ovary morphology ( J:63742 )

♀ • mutant ovaries consist predominantly of interstitial cells

absent mature ovarian follicles ( J:63742 )

♀ • mutant ovaries contain few or almost no mature follicles

small seminiferous tubules ( J:63742 )

♂ • male homozygotes display atrophic seminiferous tubules with significantly reduced spermatogenesis; some tubuli mainly have Sertoli cells

increased Leydig cell number ( J:63742 )

♂ • mutant testes display diffuse hyperplasia of Leydig cells

hematopoietic system

increased mean corpuscular volume ( J:63742 )

• at ~20 weeks of age, homozygotes display a slight increase in mean cell volume, suggestive of macrocytic red cells

• however, all other hematological parameters, including total erythrocyte counts and hemoglobin levels, remain normal and no progression to anemia is observed up to 1 year

• attempts to stress the hematopoietic system by splenectomy do not result in anemia or reduced blood cell counts

thrombocytopenia ( J:63742 )

• at ~20 weeks of age, homozygotes show a slight reduction in platelet count; however, no further decrease is noted over time

cellular

induced chromosome breakage ( J:63742 )

• homozygous mutant MEFs are hyper-responsive to the clastogenic effect of the crosslinker mitomycin C, with most cells containing >10 aberrations after treatment

spontaneous chromosome breakage ( J:63742 )

• homozygous mutant MEFs exhibit increased spontaneous chromosomal instability, with 22% of cells exhibiting aberrations vs 4% of wild-type MEFs

skeleton

skeleton phenotype ( J:63742 )

N • homozygotes display no skeletal abnormalities, as shown by radiology

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group A		DOID:0111095	OMIM:227650	J:63742