Ronfani L, Ferraguti M, Croci L, Ovitt C E, Schöler H R, Consalez G G, Bianchi M E
DIBIT, Istituto Scientifico San Raffaele, via Olgettina 58, Italy.
Development. 2001 Apr;128(8):1265-73. doi: 10.1242/dev.128.8.1265.
High mobility group 2 protein (Hmgb2) is a member of the HMGB protein family, which includes the ubiquitous Hmgb1 and the embryo-specific Hmgb3. The three proteins are more than 80% identical at the amino acid level and their biochemical properties are indistinguishable. Hmgb1 is an abundant component of all mammalian nuclei and acts as an architectural factor that bends DNA and promotes protein assembly on specific DNA targets. Cells that lack Hmgb1 can survive, although mutant mice die shortly after birth. As Hmgb2 is present in all cultured cells and is abundant in thymus, the preferred source 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 lack Hmgb2 are viable. However, male Hmgb2(-/-) mice have reduced fertility, that correlates with Sertoli and germ cell degeneration in seminiferous tubules and immotile spermatozoa. Significantly, Hmgb2 is expressed at very high levels in primary spermatocytes, while it is barely detectable in spermatogonia and elongated spermatids. This peculiar pattern of expression and the phenotype of mutants indicate that Hmgb2 has a specialised role in germ cell differentiation.
高迁移率族蛋白2（Hmgb2）是HMGB蛋白家族的成员之一，该家族还包括普遍存在的Hmgb1和胚胎特异性的Hmgb3。这三种蛋白质在氨基酸水平上的同源性超过80%，并且它们的生化特性难以区分。Hmgb1是所有哺乳动物细胞核中的一种丰富成分，作为一种结构因子，它能使DNA弯曲并促进特定DNA靶点上的蛋白质组装。缺乏Hmgb1的细胞能够存活，尽管突变小鼠在出生后不久就会死亡。由于Hmgb2存在于所有培养细胞中，并且在胸腺（HMGB蛋白的首选来源）中含量丰富，因此它被认为是Hmgb1的一种普遍存在的变体。我们发现，在成年小鼠中，Hmgb2主要局限于淋巴器官和睾丸，尽管它在胚胎发育过程中广泛表达。缺乏Hmgb2的小鼠能够存活。然而，雄性Hmgb2(-/-)小鼠的生育能力下降，这与曲细精管中的支持细胞和生殖细胞退化以及精子活力不足有关。值得注意的是，Hmgb2在初级精母细胞中表达水平非常高，而在精原细胞和延长型精子细胞中几乎检测不到。这种独特的表达模式和突变体的表型表明，Hmgb2在生殖细胞分化中具有特殊作用。
