| A targeted mutation of Nkd1 impairs mouse spermatogenesis. | |
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MedLine Citation:
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PMID: 15546883 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nkd1 is an antagonist of the canonical Wnt/beta-catenin signaling pathway. The EF-hand motif of Nkd1 is required for its inhibitory function. Early studies suggested that Nkd1 might play important roles in mouse embryonic development and tumorigenesis. We constructed Nkd1(-/-) mice whose Nkd1 protein lacked the EF-hand and was unable to inhibit Wnt/beta-catenin signaling. The homozygotes were viable and grew normally, but their fertility in males was reduced. In wild-type adult testes, Nkd1 mRNA was expressed more abundantly in the elongating spermatids than in the round spermatids. Lack of EF-hand caused reductions in the testis weight and sperm count by 30 and 60%, respectively. During testis development, Nkd1 mRNA expression started at the 25th day after birth, coincident with the onset of Wnt1 expression. Nuclear localization of beta-catenin increased in the elongating spermatids, suggesting that the mutant Nkd1 failed to inhibit the Wnt/beta-catenin pathway. These results suggest that deletion of the EF-hand from Nkd1 reduces the number of the elongating spermatids at haploid stage. In contrast, the mutant Nkd1 did not affect intestinal polyposis in Apc(Delta716) mice. |
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Authors:
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Qin Li; Tomo-O Ishikawa; Hiroyuki Miyoshi; Masanobu Oshima; Makoto M Taketo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-11-16 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 Jan |
Date Detail:
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Created Date: 2005-01-24 Completed Date: 2005-03-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 2831-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-konoé-cho, Sakyo-ku, Kyoto 606-8501, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Blotting, Western Carrier Proteins / genetics*, physiology* Gene Deletion Gene Expression Regulation, Developmental* Gene Expression Regulation, Neoplastic* Genetic Vectors Haploidy Heterozygote Homozygote Immunohistochemistry In Situ Nick-End Labeling Intestinal Polyposis / genetics Male Mice Mice, Inbred C57BL Mice, Transgenic Models, Genetic Molecular Sequence Data Mutation* Phenotype RNA / metabolism RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Sperm Count Spermatogenesis* Time Factors Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Nkd1 protein, mouse; 0/RNA, Messenger; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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