Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis
AUTOR(ES)
Yan, Wei
FONTE
National Academy of Sciences
RESUMO
Platelet-activating factor (PAF) has been shown to affect sperm motility and acrosomal function, thereby altering fertility. PAF acetylhydrolase 1b (PAFAH1B) hydrolyzes PAF and is composed of three subunits [the lissencephaly (LIS1) protein and α1 and α2 subunits] and structurally resembles a GTP-hydrolyzing protein. Besides the brain, transcripts for Lis1, α1, and α2 are localized to meiotic and early haploid germ cells. Here, we report disruptions of the α2 (Pafah1b2) and α1 (Pafah1b3) genes in mice. Male mice homozygous null for α2(α2-/-) are infertile, and spermatogenesis is disrupted at mid- or late pachytene stages of meiosis or early spermiogenesis. Whereas mice homozygous mutant for α1(α1-/-) have normal fertility and normal spermatogenesis, those with disruptions of both α1 and α2 (α1-/-α2-/-) manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis. Testicular Lis1 protein levels are up-regulated in the α2-/- and α1-/-α2-/- mice. Lowering Lis1 levels by inactivating one allele of Lis1 in α2 null or α1/α 2 null genetic backgrounds (i.e., α2-/-Lis1+/- or α1-/-α2-/-Lis1+/- mice) restored spermatogenesis and male fertility. Our data provide evidence for unique roles of the PAFAH1B complex and, particularly, the lissencephaly protein Lis1 in spermatogenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=165851Documentos Relacionados
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