Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice

• DOI: 10.1073/pnas.0308025101
• Publication Date: 2004-05-11T01:04:10Z
• Authors: Wei Yan; Lang Ma; Kathleen H. Burns; Martin M. Matzuk
• Keywords: Spermatid; Chimera (genetics); Spermiogenesis; Haploinsufficiency; Null allele

We identified a testis-specific gene encoding protein containing BTB/POZ domain and six kelch repeats, which we named k e l ch h omo og 10 (KLHL10). KLHL10 displays high evolutionary conservation in mammals, as evidenced by 98.7% amino acid identity between mouse human KLHL10. is exclusively expressed the cytoplasm of elongating elongated spermatids (steps 9-16). generated Klhl10 null allele 129S6/SvEv embryonic stem cells, obtained 47 chimeras from independent cell lines. Whereas low-percentage male only produce C57BL/6J offspring, high-percentage chimeric heterozygous males were completely infertile because disrupted spermiogenesis characterized asynchronous spermatid maturation, degeneration late spermatids, sloughing postmeiotic germ cells seminiferous epithelium, marked reduction numbers spermatids. Our data demonstrate that, like protamine-1 -2, both alleles are required for fertility that haploinsufficiency caused mutation one prevents genetic transmission mutant WT alleles.