期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：20
页码：7793-7798
DOI：10.1073/pnas.0308025101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We identified a testis-specific gene encoding a protein containing a BTB/POZ domain and six kelch repeats, which we named kelch homolog 10 (KLHL10). KLHL10 displays high evolutionary conservation in mammals, as evidenced by 98.7% amino acid identity between mouse and human KLHL10. KLHL10 is exclusively expressed in the cytoplasm of elongating and elongated spermatids (steps 9-16). We generated a Klhl10 null allele in 129S6/SvEv mouse embryonic stem cells, and obtained 47 chimeras from six independent embryonic stem cell lines. Whereas low-percentage male chimeras only produce C57BL/6J offspring, high-percentage chimeric and heterozygous males were completely infertile because of disrupted spermiogenesis characterized by asynchronous spermatid maturation, degeneration of late spermatids, sloughing of postmeiotic germ cells from the seminiferous epithelium, and marked reduction in the numbers of late spermatids. Our data demonstrate that, like protamine-1 and -2, both alleles of Klhl10 are required for male fertility and that haploinsufficiency caused by a mutation in one allele of Klhl10 prevents genetic transmission of both mutant and WT alleles.
