Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice.
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.
Nakane
Hironobu
H
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
Hirota
Seiichi
S
Brooks
Philip J
PJ
Nakabeppu
Yusaku
Y
Nakatsu
Yoshimichi
Y
Nishimune
Yoshitake
Y
Iino
Akihiro
A
Tanaka
Kiyoji
K
D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D004195:Disease Models, Animal; D006130:Growth Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D013091:Spermatogenesis; D013094:Spermatozoa / Q000473:pathology; D013733:Testicular Diseases / Q000235:genetics* / Q000473:pathology; D051760:Xeroderma Pigmentosum Group A Protein / Q000502:physiology*
D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse
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