학술논문
Mutation of the Thap4 gene causes dwarfism and testicular anomalies in rats and mice.
Document Type
Academic Journal
Author
Katayama K; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Ito J; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Murakami R; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Yamashita A; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Sasajima H; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Narahashi S; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Chiba J; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Yamamoto I; Laboratory of Veterinary Biochemistry, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Fujii W; Laboratory of Biomedical Science, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.; Tochigi Y; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.; Suzuki H; Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan. hiroetsu@nvlu.ac.jp.
Source
Publisher: Springer-Verlag Country of Publication: United States NLM ID: 9100916 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1777 (Electronic) Linking ISSN: 09388990 NLM ISO Abbreviation: Mamm Genome Subsets: MEDLINE
Subject
Language
English
Abstract
The petit (pet) locus is associated with dwarfism, testicular anomalies, severe thymic hypoplasia, and high postnatal lethality, which are inherited in autosomal recessive mode of inheritance in rats with a Wistar strain genetic background. Linkage analysis localized the pet locus between 98.7 Mb and 101.2 Mb on rat chromosome 9. Nucleotide sequence analysis identified 2 bp deletion in exon 2 of the Thap4 gene as the causative mutation for pet. This deletion causes a frameshift and premature termination codon, resulting in a truncated THAP4 protein lacking approximately two-thirds of the C-terminal side. Thap4 is expressed in various organs, including the testis and thymus in rats. To elucidate the biological function of THAP4 in other species, we generated Thap4 knockout mice lacking exon 2 of the Thap4 gene through genome editing. Thap4 knockout mice also exhibited dwarfism and small testis but did not show high postnatal lethality. Thymus weights of adult Thap4 knockout male mice were significantly higher compared to wild-type male mice. Although Thap4 knockout male mice were fertile, their testis contained seminiferous tubules with spermatogenesis and degenerative seminiferous tubules lacking germ cells. Additionally, we observed vacuoles in seminiferous tubules, and clusters of cells in the lumen in seminiferous tubules in Thap4 knockout male mice. These results demonstrate that spontaneous mutation of Thap4 gene in rats and knockout of Thap4 gene in mice both cause dwarfism and testicular anomalies. Thap4 gene in rats and mice is essential for normal testicular development, maintaining spermatogenesis throughout the entire region of seminiferous tubules.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)