Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints

0525133 - ÚMG 2021 RIV US eng J - Článek v odborném periodiku
Mihola, Ondřej - Kobets, Tetyana - Křivánková, Klára - Linhartová, Eliška - Gašić, Srdjan - Schimenti, J.C. - Trachtulec, Zdeněk
Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints.
Chromosoma. Roč. 129, č. 1 (2020), s. 69-82. ISSN 0009-5915. E-ISSN 1432-0886
Grant CEP: GA ČR GA16-19158S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395
Institucionální podpora: RVO:68378050
Klíčová slova: Fertility * Transgene * Interspecific hybrid * Spermatogenesis * Proteasome
Obor OECD: Genetics and heredity (medical genetics to be 3)
Impakt faktor: 4.316, rok: 2020
Způsob publikování: Omezený přístup
https://link.springer.com/article/10.1007/s00412-019-00730-8

Long transgenes are often used in mammalian genetics, e.g., to rescue mutations in large genes. In the course of experiments addressing the genetic basis of hybrid sterility caused by meiotic defects in mice bearing different alleles of Prdm9, we discovered that introduction of copy-number variation (CNV) via two independent insertions of long transgenes containing incomplete Prdm9 decreased testicular weight and epididymal sperm count. Transgenic animals displayed increased occurrence of seminiferous tubules with apoptotic cells at 18 days postpartum (dpp) corresponding to late meiotic prophase I, but not at 21 dpp. We hypothesized that long transgene insertions could cause asynapsis, but the immunocytochemical data revealed that the adult transgenic testes carried a similar percentage of asynaptic pachytene spermatocytes as the controls. These transgenic spermatocytes displayed less crossovers but similar numbers of unrepaired meiotic breaks. Despite slightly increased frequency of metaphase I spermatocytes with univalent chromosome(s) and reduced numbers of metaphase II spermatocytes, cytological studies did not reveal increased apoptosis in tubules containing the metaphase spermatocytes, but found an increased percentage of tubules carrying apoptotic spermatids. Sperm counts of subfertile animals inversely correlated with the transcription levels of the Psmb1 gene encoded within these two transgenes. The effect of the transgenes was dependent on sex and genetic background. Our results imply that the fertility of transgenic hybrid animals is not compromised by the impaired meiotic synapsis of homologous chromosomes, but can be negatively influenced by the increased expression of the introduced genes.
Trvalý link: http://hdl.handle.net/11104/0309342