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Publication : Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice.

First Author  Nakane H Year  2020
Journal  Biomed Res Volume  41
Issue  5 Pages  237-242
PubMed ID  33071259 Mgi Jnum  J:333236
Mgi Id  MGI:6754763 Doi  10.2220/biomedres.41.237
Citation  Nakane H, et al. (2020) Autophagy induction on impaired spermatogenesis of xeroderma pigmentosum group A gene-deficient mice. Biomed Res 41(5):237-242
abstractText  Xeroderma pigmentosum (XP) involves a defect in the initial step of nucleotide excision repair (NER) and consists of eight genetic complementation groups (groups A-G and a variant). XP group A (XPA) patients have a high incidence of UV-induced skin tumors, immature testicular development, and neurological symptoms. In an earlier study, we have shown that XP group A (Xpa) gene-knockout mice (Xpa(-/-) mice) were highly sensitive to UV-induced skin carcinogenesis with a defect in NER and were highly susceptibility to spontaneous tumorigenesis with impaired spermatogenesis. However, the pathology of impaired spermatogenesis in Xpa(-/-) mice is unknown. To unravel the underlying pathology, we made a concerted effort using the testis of 3-month-old Xpa(-/-) mice. We found many large vacuoles in the seminiferous tubules of 3-month old Xpa(-/-) mice, while there were no large vacuoles in that of Xpa(+/+) mice. Immunohistochemistry of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, showed degenerating cells with intense signal of LC3 in the seminiferous tubules, and immunoblotting revealed induction of LC3-II in the 3-month-old Xpa(-/-) mice. The results of the present study suggest autophagy induction as the possible mechanism underlying the impaired spermatogenesis in Xpa(-/-) mice. Therefore, Xpa(-/-) mice could be a useful model for investigating aging and male infertility with low expression of XPA.
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