Impaired spermatogenesis and male fertility defects in CIZ/Nmp4-disrupted mice.
CIZ (Cas interacting zinc finger protein), also called Nmp4 (nuclear matrix protein 4), is a nucleo-cytoplasmic shuttling transcription factor that regulates the expression of collagen and matrix metalloproteinases. CIZ/Nmp4 was originally cloned by its binding to p130(Cas), a focal adhesion protein, and was recently shown to suppress BMP2 (bone mophogenetic protein 2) signalling. To explore the physiological role of CIZ/Nmp4, we disrupted CIZ/Nmp4-gene by inserting beta-galactosidase and neomycin resistance genes into the 2nd exon of CIZ/Nmp4-gene, which is utilized by all the sequenced alternative forms. CIZ-/- mice were born and grew to adulthood. Although they tend to be smaller than wild-type mice, no pathological abnormality was observed except in the testis. Histological analysis of the testes revealed variable degrees of spermatogenic cell degeneration within the seminiferous tubules of CIZ-/- mice, resembling the histology of the 'Germinal-cell aplasia with focal spermatogenesis'. Some of the CIZ-/- male mice developed infertility. TUNEL assay on testis sections revealed an increased occurrence of apoptosis of spermatogenic cells in the testes of CIZ-/- mice. CIZ/Nmp4 was co-localized with Smad1 in the testis, suggesting that a disregulation of BMP signalling could cause these phenotypes. These results suggest that CIZ/Nmp4 plays roles in the progress and the maintenance of spermatogenesis.
Nakamoto
Tetsuya
T
Department of Haematology & Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. nakamoto@scripps.edu
Shiratsuchi
Akiko
A
Oda
Hideaki
H
Inoue
Keiichi
K
Matsumura
Tomoko
T
Ichikawa
Motoshi
M
Saito
Toshiki
T
Seo
Sachiko
S
Maki
Kazuhiro
K
Asai
Takashi
T
Suzuki
Takahiro
T
Hangaishi
Akira
A
Yamagata
Tetsuya
T
Aizawa
Shinichi
S
Noda
Masaki
M
Nakanishi
Yoshinobu
Y
Hirai
Hisamaru
H
D000375:Aging; D000483:Alleles; D000818:Animals; D049628:Body Size / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D016678:Genome; D007248:Infertility, Male / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009355:Neomycin; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D051785:Smad Proteins; D051898:Smad1 Protein; D013091:Spermatogenesis; D013234:Stem Cells / Q000166:cytology; D013737:Testis / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology*; D001616:beta-Galactosidase
D004268:DNA-Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C499081:Zfp384 protein, mouse; D001616:beta-Galactosidase; D009355:Neomycin