Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice

Hironobu Nakane, Seiichi Hirota, Philip J. Brooks, Yusaku Nakabeppu, Yoshimichi Nakatsu, Yoshitake Nishimune, Akihiro Iino, Kiyoji Tanaka

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1938-1950
Number of pages13
JournalDNA Repair
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 1 2008

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Xeroderma Pigmentosum
Spermatogenesis
Tumors
Skin
Carcinogenesis
Genes
Pathogens
Repair
Nucleotides
Aging of materials
Specific Pathogen-Free Organisms
Gene Knockout Techniques
Sexual Development
Seminiferous Tubules
Incidence
Knockout Mice
DNA Repair
Spermatozoa
Testis
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice. / Nakane, Hironobu; Hirota, Seiichi; Brooks, Philip J.; Nakabeppu, Yusaku; Nakatsu, Yoshimichi; Nishimune, Yoshitake; Iino, Akihiro; Tanaka, Kiyoji.

In: DNA Repair, Vol. 7, No. 12, 01.12.2008, p. 1938-1950.

Research output: Contribution to journalArticle

Nakane, Hironobu ; Hirota, Seiichi ; Brooks, Philip J. ; Nakabeppu, Yusaku ; Nakatsu, Yoshimichi ; Nishimune, Yoshitake ; Iino, Akihiro ; Tanaka, Kiyoji. / Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice. In: DNA Repair. 2008 ; Vol. 7, No. 12. pp. 1938-1950.
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