Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice |
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Authors: | Nakane Hironobu Hirota Seiichi Brooks Philip J Nakabeppu Yusaku Nakatsu Yoshimichi Nishimune Yoshitake Iino Akihiro Tanaka Kiyoji |
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Institution: | Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan. mnakane@med.tottori-u.ac.jp |
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Abstract: | We have reported that xeroderma pigmentosum group A (Xpa) gene-knockout mice Xpa (−/−) mice] are deficient in nucleotide excision repair (NER) and highly sensitive to UV-induced skin carcinogenesis. Although xeroderma pigmentosum group A patients show growth retardation, immature sexual development, and neurological abnormalities as well as a high incidence of UV-induced skin tumors, Xpa (−/−) mice were physiologically and behaviorally normal. In the present study, we kept Xpa (−/−) mice for 2 years under specific pathogen-free (SPF) conditions and found that the testis diminished in an age-dependent manner, and degenerating seminiferous tubules and no spermatozoa were detected in the 24-month-old Xpa (−/−) mice. In addition, a higher incidence of spontaneous tumorigenesis was observed in the 24-month-old Xpa (−/−) mice compared to Xpa (+/+) controls. Xpa (−/−) mice provide a useful model for investigating the aging and internal tumor formation in XPA patients. |
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Keywords: | Xeroderma pigmentosum (XP) Nucleotide excision repair (NER) Spermatogenesis Spontaneous tumorigenesis Knockout mice |
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