DAZL Knockout Pigs as Recipients for Spermatogonial Stem Cell Transplantation.
DAZL Knockout Pigs as Recipients for Spermatogonial Stem Cell Transplantation.
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Spermatogonial stem cell (SSC) transplantation into the testis of a germ cell (GC)-depleted surrogate allows transmission of donor genotype via donor-derived sperm produced by the recipient. Transplantation of gene-edited SSCs provides an approach to propagate gene-edited large animal models. DAZL is a conserved RNA-binding protein important for GC development, and DAZL knockout (KO) causes defects in GC commitment and differentiation. We characterized DAZL-KO pigs as SSC transplantation recipients. While there were GCs in 1-week-old (wko) KO, complete GC depletion was observed by 10 wko. Donor GCs were transplanted into 18 DAZL-KO recipients at 10–13 wko. At sexual maturity, semen and testes were evaluated for transplantation efficiency and spermatogenesis. Approximately 22% of recipient seminiferous tubules contained GCs, including elongated spermatids and proliferating spermatogonia. The ejaculate of 89% of recipients contained sperm, exclusively from donor origin. However, sperm concentration was lower than the wild-type range. Testicular protein expression and serum hormonal levels were comparable between DAZL-KO and wild-type. Intratesticular testosterone and Leydig cell volume were increased, and Leydig cell number decreased in transplanted DAZL-KO testis compared to wild-type. In summary, DAZL-KO pigs support donor-derived spermatogenesis following SSC transplantation, but low spermatogenic efficiency currently limits their use for the production of offspring.
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DOI：
10.1073/pnas.2010102117
发表时间：
2020-09-29
影响因子：
11.1
作者：
Ciccarelli M;Giassetti MI;Miao D;Oatley MJ;Robbins C;Lopez-Biladeau B;Waqas MS;Tibary A;Whitelaw B;Lillico S;Park CH;Park KE;Telugu B;Fan Z;Liu Y;Regouski M;Polejaeva IA;Oatley JM
通讯作者：
Oatley JM
影响因子：
8.3
作者：
Goossens, E.;Jahnukainen, K.;Stukenborg, J. B.
通讯作者：
Stukenborg, J. B.
DOI：
10.12703/r/10-55
发表时间：
2021
期刊：
Faculty reviews
影响因子：
--
作者：
Doungkamchan C;Orwig KE
通讯作者：
Orwig KE
影响因子：
3.6
作者：
Brinster, CJ;Ryu, BY;Orwig, KE
通讯作者：
Orwig, KE
影响因子：
3.6
作者：
Herrid, Muren;Olejnik, Jeanette;Hill, Jonathan R.
通讯作者：
Hill, Jonathan R.