Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2

High mobility group 2 protein (Hmgb2) is a member of the HMGB protein famil y, which includes the ubiquitous Hmgb1 and the embryo-specific Hmgb3. The t hree proteins are more than 80% identical at the amino acid level and their biochemical properties are indistinguishable. Hmgb1 is an abundant compone nt of all mammalian nuclei and acts as an architectural factor that bends D NA acid promotes protein assembly on specific DNA targets. Cells that lack Hmgb1 can survive, although mutant mice die shortly after birth. As Hmgb2 i s present in all cultured cells and is abundant in thymus, the preferred so urce for HMGB proteins, it was considered a ubiquitous variant of Hmgb1. We show that in adult mice Hmgb2 is restricted mainly to lymphoid organs and testes, although it is widely expressed during embryogenesis, Mice that lac k Hmgb2, are viable. However, male Hmgb2(-/-) mice have reduced fertility t hat correlates with Sertoli and germ cell degeneration in seminiferous tubu les and immotile spermatozoa. Significantly, Hmgb2 is expressed at very hig h levels in primary spermatocytes, while it is barely detectable in spermat ogonia and elongated spermatids. This peculiar pattern of expression and th e phenotype of mutants indicate that Hmgb2 has a specialised role in germ c ell differentiation.