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Background  HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1α, HP1β and HP1γ, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1γ using a gene-targeted mouse.    Results  While targeting the  Cbx3  gene (encoding the HP1γ protein) with a conditional targeting vector, we generated a hypomorphic allele ( Cbx3   hypo  ), which resulted in much reduced (barely detectable) levels of HP1γ protein. Homozygotes for the hypomorphic allele ( Cbx3   hypo / hypo  ) are rare, with only 1% of  Cbx3   hypo / hypo   animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype). The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p) in  Cbx3   hypo / hypo   testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in  Cbx3   hypo / hypo   germ cells.    Conclusions  The  Cbx3  gene product (the HP1γ protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The  Cbx3   hypo / hypo   spermatogenesis defect is similar to that found in  Miwi2  and  Dnmt3L  mutants. The  Cbx3  gene-targeted mice generated in this study provide an appropriate model for the study of HP1γ in transposon silencing and parental imprinting.

HP1γ function is required for male germ cell survival and spermatogenesis