TY - JOUR
T1 - Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice
AU - Nakane, Hironobu
AU - Hirota, Seiichi
AU - Brooks, Philip J.
AU - Nakabeppu, Yusaku
AU - Nakatsu, Yoshimichi
AU - Nishimune, Yoshitake
AU - Iino, Akihiro
AU - Tanaka, Kiyoji
PY - 2008/12/1
Y1 - 2008/12/1
N2 - 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.
AB - 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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U2 - 10.1016/j.dnarep.2008.08.003
DO - 10.1016/j.dnarep.2008.08.003
M3 - Article
C2 - 18790090
AN - SCOPUS:55149113452
VL - 7
SP - 1938
EP - 1950
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
IS - 12
ER -