title: HP1gamma function is required for male germ cell survival and spermatogenesis.
abstract: HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1alpha, HP1beta and HP1gamma, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1gamma using a gene-targeted mouse.
  
  
  
  While targeting the Cbx3 gene (encoding the HP1gamma protein) with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo), which resulted in much reduced (barely detectable) levels of HP1gamma protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo) are rare, with only 1% of Cbx3hypo/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 Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells.
  
  
  
  The Cbx3 gene product (the HP1gamma protein) has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/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 HP1gamma in transposon silencing and parental imprinting.
authors.affiliation: Division of Immunoepigenetics, Department of Immunology and Cell Biology, Research Center Borstel, D-23845 Borstel, Germany. psingh@fz-borstel.de.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Brown
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullwinkel
authors.forename: Bettina
authors.initials: B
authors.lastname: Baron-Lühr
authors.forename: Mustafa
authors.initials: M
authors.lastname: Billur
authors.forename: Philipp
authors.initials: P
authors.lastname: Schneider
authors.forename: Heinz
authors.initials: H
authors.lastname: Winking
authors.forename: Prim B
authors.initials: PB
authors.lastname: Singh