HP1gamma function is required for male germ cell survival and spermatogenesis

Jeremy P Brown, Jörn Bullwinkel, Bettina Baron-Lühr, Mustafa Billur, Philipp Schneider, Heinz Winking, Prim B Singh

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Abstract

BACKGROUND: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)9
JournalEpigenetics and Chromatin
Volume3
Issue number1
DOIs
Publication statusPublished - Apr 27 2010

Keywords

  • Journal Article

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    Brown, J. P., Bullwinkel, J., Baron-Lühr, B., Billur, M., Schneider, P., Winking, H., & Singh, P. B. (2010). HP1gamma function is required for male germ cell survival and spermatogenesis. Epigenetics and Chromatin, 3(1), 9. https://doi.org/10.1186/1756-8935-3-9