Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints
Jazyk angličtina Země Rakousko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
31940063
DOI
10.1007/s00412-019-00730-8
PII: 10.1007/s00412-019-00730-8
Knihovny.cz E-zdroje
- Klíčová slova
- Fertility, Interspecific hybrid, Proteasome, Spermatogenesis, Transgene,
- MeSH
- apoptóza genetika MeSH
- dvouřetězcové zlomy DNA MeSH
- fertilita genetika MeSH
- genetické pozadí MeSH
- kontrolní body buněčného cyklu genetika MeSH
- myši MeSH
- pachytenní stadium genetika MeSH
- počet spermií MeSH
- spermatocyty metabolismus MeSH
- testis anatomie a histologie metabolismus MeSH
- transgeny * MeSH
- variabilita počtu kopií segmentů DNA * MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
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Science. 2010 Feb 12;327(5967):835 PubMed
Nat Rev Genet. 2014 May;15(5):321-34 PubMed
Curr Biol. 2011 May 10;21(9):787-93 PubMed
Mamm Genome. 2005 Nov;16(11):838-46 PubMed
Cell Death Dis. 2016 Jul 28;7(7):e2317 PubMed
Sci Rep. 2019 Mar 26;9(1):5158 PubMed
Sci Rep. 2017 Sep 6;7(1):10733 PubMed
Nature. 2019 Feb;566(7742):105-109 PubMed
Pathog Glob Health. 2017 Dec;111(8):424-435 PubMed
Xenotransplantation. 2005 Mar;12(2):142-8 PubMed
Science. 2009 Jan 16;323(5912):373-5 PubMed
Sci Rep. 2017 Jul 12;7(1):5230 PubMed
Biol Reprod. 2007 Jan;76(1):149-63 PubMed
Nucleic Acids Res. 1999 Jan 15;27(2):526-31 PubMed
Folia Biol (Praha). 2000;46(1):31-41 PubMed
Genome Res. 2019 Jul;29(7):1078-1086 PubMed
Anal Biochem. 1999 May 15;270(1):41-9 PubMed
Mol Cell Biol. 2006 Apr;26(8):2999-3007 PubMed
Compr Physiol. 2019 Mar 14;9(2):665-714 PubMed
Science. 2010 Feb 12;327(5967):876-9 PubMed
Trends Parasitol. 2006 May;22(5):197-202 PubMed
Cytogenet Cell Genet. 1987;45(2):70-4 PubMed
Genome Res. 2001 Jan;11(1):137-42 PubMed
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):891-6 PubMed
Folia Biol (Praha). 2017;63(1):27-30 PubMed
Elife. 2018 Mar 14;7: PubMed
Cell Rep. 2018 Oct 23;25(4):1027-1039.e6 PubMed
J Cell Biol. 1977 Jul;74(1):68-85 PubMed
PLoS Genet. 2012;8(11):e1003044 PubMed
Reprod Biol Endocrinol. 2003 Feb 06;1:11 PubMed
Science. 2011 Feb 18;331(6019):916-20 PubMed
PLoS One. 2014 Apr 22;9(4):e95806 PubMed
Chromosoma. 2016 Jun;125(2):227-35 PubMed
G3 (Bethesda). 2015 Dec 18;6(2):263-79 PubMed
Nature. 2003 Oct 30;425(6961):917-25 PubMed
Science. 2010 Feb 12;327(5967):836-40 PubMed
Nature. 2005 Nov 17;438(7066):374-8 PubMed
Genetics. 1999 Apr;151(4):1569-79 PubMed
Sci Rep. 2016 Jun 29;6:29081 PubMed
Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E468-77 PubMed
Genetics. 2008 Mar;178(3):1777-84 PubMed
Cell. 2013 May 23;153(5):1012-24 PubMed
Mol Endocrinol. 1999 Jun;13(6):841-50 PubMed
