Expression of cell-cycle regulator CDK2-associating protein 1 (p12 CDK2AP1) in transgenic mice induces testicular and ovarian atrophy in vivo

M. L. Figueiredo, S. Dayan, Y. Kim, J. McBride, T. S. Kupper, D. T.W. Wong

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The novel cell-cycle regulator p12COK2Ap1 (p12) gene encodes a cyclin-dependent kinase 2 (CDK2) partner that participates in cell-cycle regulation, apoptosis, and proliferation. CDK2 has been implicated in maintenance of gonadal homeostasis, as knockout mice display reproductive abnormalities. To investigate the role of p12 in homeostasis of gonadal tissues in vivo, we generated a transgenic mouse model driven by the human keratin 14 promoter, reported to target transgene expression to gonadal tissues and also stratified epithelia. Overexpression of the transgene was associated with a gonadal atrophy phenotype in mice of both sexes, yet fertility was not impaired. Histological evaluation of testes showed seminiferous tubule degeneration and decreased tubule diameter. Female transgenic mice had small ovaries, with a higher number of atretic follicles/mm2 as compared to control nontransgenic mice. Also observed was increased germ cell apoptosis in both sexes (TUNEL). These results suggest that overexpression of p12 leads to testicular and ovarian abnormalities, a phenotype closely related to that of cdk2-/- mice. In combination, these observations suggest that the p12/CDK2 signaling pathways are carefully orchestrated to maintain proper gonadal tissue homeostasis. We suggest that the mechanisms of this regulation may be through p12-mediated altered expression of gonadal-specific genes and apoptotic pathways.

Original languageEnglish (US)
Pages (from-to)987-997
Number of pages11
JournalMolecular Reproduction and Development
Volume73
Issue number8
DOIs
StatePublished - Aug 1 2006

Keywords

  • Altered growth
  • Apoptosis
  • CDK2AP1
  • Gonadal

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

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