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Published on: February 6, 2018
Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2
L Ronfani1, M Ferraguti, L Croci
1DIBIT, Istituto Scientifico San Raffaele, via Olgettina 58, Italy.
Abstract:
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.
Insights
High mobility group 2 protein (Hmgb2) is crucial for male fertility and germ cell development. Studies show Hmgb2
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- High mobility group 2 protein (Hmgb2) belongs to the HMGB family, sharing high amino acid identity with Hmgb1 and Hmgb3.
- Hmgb1 is a ubiquitous nuclear architectural factor, essential for mammalian development.
- Hmgb2 was previously considered a ubiquitous variant of Hmgb1 due to its presence in cultured cells and thymus.
Purpose of the Study:
- To investigate the specific expression pattern and functional role of Hmgb2 in adult mice.
- To determine the consequences of Hmgb2 deficiency on male reproductive health and fertility.
Main Methods:
- Analysis of Hmgb2 expression in adult mouse tissues.
- Phenotypic analysis of Hmgb2-deficient (Hmgb2(-/-)) mice, focusing on reproductive organs.
- Histological examination of seminiferous tubules and sperm motility assessment.
Main Results:
- Hmgb2 expression is restricted to lymphoid organs and testes in adult mice, contrasting with its broad embryonic expression.
- Hmgb2(-/-) mice are viable but exhibit reduced male fertility.
- Deficiency in Hmgb2 leads to degeneration of Sertoli and germ cells, and immotile spermatozoa.
- Hmgb2 is highly expressed in primary spermatocytes but minimally in spermatogonia and elongated spermatids.
Conclusions:
- Hmgb2 plays a specialized and critical role in male germ cell differentiation and fertility.
- The distinct expression pattern of Hmgb2 during spermatogenesis underlies its specific function in reproductive health.
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