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
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant numbers: 18591782, 20591898 to H.N. and 17109006 to K.T.), and by a Grant for Solution Oriented Research for Science and Technology (SORST) of Japan Science and Technology Agency (JST) to K.T. We thank Dr. Junji Tsuchida for helpful advice, and Akinori Fukuyama, Kenji Morihara and Toshio Kameie for excellent technical support.
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.
KW - Knockout mice
KW - Nucleotide excision repair (NER)
KW - Spermatogenesis
KW - Spontaneous tumorigenesis
KW - Xeroderma pigmentosum (XP)
UR - https://www.scopus.com/pages/publications/55149113452
UR - https://www.scopus.com/pages/publications/55149113452#tab=citedBy
U2 - 10.1016/j.dnarep.2008.08.003
DO - 10.1016/j.dnarep.2008.08.003
M3 - Article
C2 - 18790090
AN - SCOPUS:55149113452
SN - 1568-7864
VL - 7
SP - 1938
EP - 1950
JO - DNA Repair
JF - DNA Repair
IS - 12
ER -