Author:
Miyata Haruhiko,Castaneda Julio M.,Fujihara Yoshitaka,Yu Zhifeng,Archambeault Denise R.,Isotani Ayako,Kiyozumi Daiji,Kriseman Maya L.,Mashiko Daisuke,Matsumura Takafumi,Matzuk Ryan M.,Mori Masashi,Noda Taichi,Oji Asami,Okabe Masaru,Prunskaite-Hyyrylainen Renata,Ramirez-Solis Ramiro,Satouh Yuhkoh,Zhang Qian,Ikawa Masahito,Matzuk Martin M.
Abstract
Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others.
Funder
HHS | NIH | National Institute of Child Health and Human Development
Ministry of Education, Culture, Sports, Science, and Technology
Wellcome Trust
HHS | NIH | National Human Genome Research Institute
Publisher
Proceedings of the National Academy of Sciences
Cited by
133 articles.
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