Absence of the DNA-/RNA-binding protein MSY2 results in male and female infertility.
MSY2, a germ-cell-specific member of the Y-box family of DNA-/RNA-binding proteins, is proposed to function as a coactivator of transcription in the nucleus and to stabilize and store maternal and paternal mRNAs in the cytoplasm. In mice lacking Msy2, a normal Mendelian ratio is observed after matings between heterozygotes with equal numbers of phenotypically normal but sterile male and female homozygotes (Msy2-/-). Spermatogenesis is disrupted in postmeiotic null germ cells with many misshapen and multinucleated spermatids, and no spermatozoa are detected in the epididymis. Apoptosis is increased in the testes of homozygotes, and real-time RT-PCR assays reveal large reductions in the mRNA levels of postmeiotic male germ cell mRNAs and smaller reductions of meiotic germ cell transcripts. In females, there is no apparent decrease in either the number of follicles or their morphology in ovaries obtained from 2- and 8-day-old Msy2-/- mice. In contrast, follicle number and progression are reduced in 21-day-old Msy2-/- ovaries. In adult Msy2-/- females, oocyte loss increases, anovulation is observed, and multiple oocyte and follicle defects are seen. Thus, Msy2 represents one of a small number of germ-cell-specific genes whose deletion leads to the disruption of both spermatogenesis and oogenesis.
Yang
Juxiang
J
Center for Research on Reproduction and Women's Health and Department of Biology, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Medvedev
Sergey
S
Yu
Junying
J
Tang
Linda C
LC
Agno
Julio E
JE
Matzuk
Martin M
MM
Schultz
Richard M
RM
Hecht
Norman B
NB
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D020287:In Situ Nick-End Labeling; D007246:Infertility; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D009866:Oogenesis / Q000502:physiology; D010053:Ovary / Q000002:abnormalities / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000002:abnormalities / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C116047:Ybx2 protein, mouse