Fanconi Anemia (FA) is an autosomal recessive disorder characterized by cellular 
hypersensitivity to DNA cross-linking agents. Recent studies suggest that FA 
proteins share a common pathway with BRCA proteins. To study the in vivo role of 
the FA group A gene (Fanca), gene-targeting techniques were used to generate 
Fanca(tm1Hsc) mice in which Fanca exons 1-6 were replaced by a 
beta-galactosidase reporter construct. Fanca(tm1.1Hsc) mice were generated by 
Cre-mediated removal of the neomycin cassette in Fanca(tm1Hsc) mice. 
Fanca(tm1.1Hsc) homozygotes display FA-like phenotypes including growth 
retardation, microphthalmia and craniofacial malformations that are not found in 
other Fanca mouse models, and the genetic background affects manifestation of 
certain phenotypes. Both male and female mice homozygous for Fanca mutation 
exhibit hypogonadism, and homozygous females demonstrate premature reproductive 
senescence and an increased incidence of ovarian cysts. We showed that fertility 
defects in Fanca(tm1.1Hsc) homozygotes might be related to a diminished 
population of primordial germ cells (PGCs) during migration into the gonadal 
ridges. We also found a high level of Fanca expression in pachytene 
spermatocytes. Fanca(tm1Hsc) homozygous males exhibited an elevated frequency of 
mispaired meiotic chromosomes and increased apoptosis in germ cells, implicating 
a role for Fanca in meiotic recombination. However, the localization of Rad51, 
Brca1, Fancd2 and Mlh1 appeared normal on Fanca(tm1Hsc) homozygous meiotic 
chromosomes. Taken together, our results suggest that the FA pathway plays a 
role in the maintenance of reproductive germ cells and in meiotic recombination.