Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice
| العنوان: | Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice |
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| المؤلفون: | Yuhkoh Satouh, Ayako Isotani, Qian Zhang, Martin M. Matzuk, Ramiro Ramirez-Solis, Takafumi Matsumura, Haruhiko Miyata, Asami Oji, Julio M Castaneda, Renata Prunskaite-Hyyryläinen, Daiji Kiyozumi, Masaru Okabe, Daisuke Mashiko, Masahito Ikawa, Ryan M. Matzuk, Masashi Mori, Denise R. Archambeault, Zhifeng Yu, Yoshitaka Fujihara, Taichi Noda, Maya Kriseman |
| المصدر: | Proceedings of the National Academy of Sciences. 113:7704-7710 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genomics, Biology, Genome, genetically modified mice, Conserved sequence, Mice, 03 medical and health sciences, 0302 clinical medicine, Genome editing, spermatozoa, Testis, Animals, genome editing, CRISPR, Spermatogenesis, Gene, Mice, Knockout, Genetics, Multidisciplinary, Biological Evolution, Phenotype, Fertility, 030104 developmental biology, Fertilization, Knockout mouse, Female, CRISPR-Cas Systems, Genetic Engineering, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97c42d6a95456d0d20f31496a9b438a9 https://doi.org/10.1073/pnas.1608458113 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....97c42d6a95456d0d20f31496a9b438a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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