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- Title
Hypomorphic mutation in an essential cell-cycle kinase causes growth retardation and impaired spermatogenesis.
- Authors
Jung Min Kim; Takemoto, Naofumi; Arai, Ken-Ichi; Masai, Hisao
- Abstract
Cdc7 kinase is essential for initiation of DNA replication. Cdc7-/- mouse embryonic stem (ES) cells are non-viable but their growth can be rescued by an ectopically expressed transgene (Cdc7-/-tg). Here we report that, despite the normal growth capability of Cdc7-/-tg ES cells, the mice with the identical genetic background exhibit growth retardation. Concomitantly, Cdc7-/-tg embryonic fibroblasts (MEFs) display delayed S phase entry and slow S phase progression. Furthermore, spermatogenesis of Cdc7-/-tg mice is disrupted prior to pachytene stage of meiotic prophase I. The impairment in spermatogenesis correlates with the extremely low level of Cdc7 protein in testes, and is rescued by introducing an additional allele of transgene, which results in increase of Cdc7 expression. The increased level of Cdc7 also recovers the growth of Cdc7-/-tg MEFs and mice, indicating that the developmental abnormalities of Cdc7-/-tg mice are due to insufficiency of Cdc7 protein. Our results indicate the requirement of a critical level of a cell-cycle regulator for mouse development and provide genetic evidence that Cdc7 plays essential roles in meiotic processes in mammals.
- Subjects
GENETIC mutation; CELL cycle; SPERMATOGENESIS; DNA replication; CELL proliferation; EMBRYONIC stem cells
- Publication
EMBO Journal, 2003, Vol 22, Issue 19, p5260
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/cdg497