title: An ENU-induced mutation in the mouse Rnf212 gene is associated with male meiotic failure and infertility.
abstract: The ENU-induced repro57 mutation was identified in an unbiased screen for the discovery of novel genes for fertility. Male repro57 homozygous mice are infertile and exhibit significantly reduced testis weight compared with WT mice. Histological examination of mutant testes revealed that spermatocytes degenerated during late prophase, and no mature spermatozoa were found in the seminiferous epithelium, suggesting that infertility is caused by the arrest of spermatogenesis at late meiotic prophase. Consistent with this hypothesis, the number of foci with MLH1, a protein essential for crossing over, is greatly reduced in repro57 mutant spermatocytes, which also lack chiasmata between homologs and exhibit premature dissociation of XY chromosomes. In repro57 mutant mice, we identified a mutation in the Rnf212 gene, encoding Ring finger protein 212. The overall phenotype of repro57 mice is consistent with the recently reported phenotype of the Rnf212 knockout mice; slight differences may be due to genetic background effects. Thus, the repro57 nonsense mutation provides a new allele of the mouse Rnf212 gene.
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kouyou
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Anuj
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Chikushi
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Mary
authors.initials: M
authors.lastname: Ann Handel
authors.affiliation: Graduate School of Natural Science and TechnologyOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, JapanThe Jackson Laboratory600 Main Street, Bar Harbor, Maine 04609, USAGraduate School of Environmental and Life ScienceOkayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan tkunieda@cc.okayama-u.ac.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kunieda
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005038:Ethylnitrosourea / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007248:Infertility, Male / Q000209:etiology* / Q000473:pathology; D008025:Ligases / Q000502:physiology*; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020125:Mutation, Missense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis
chemical_list: D000477:Alkylating Agents; D012333:RNA, Messenger; D008025:Ligases; C581307:Rnf212 protein, mouse; D005038:Ethylnitrosourea
keywords: crossing over; meiosis; mouse; repro57; spermatogenesis