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Testes of DAZL null neonatal sheep lack prospermatogonia but maintain normal somatic cell morphology and marker expression

journal contribution
posted on 2023-05-03, 18:40 authored by Zachariah McLean, Sarah ApplebySarah Appleby, Jingwei WeiJingwei Wei, Russell Snell, Björn ObackBjörn Oback
Multiplying the germline would increase the number of offspring that can be produced from selected animals, accelerating genetic improvement for livestock breeding. This could be achieved by producing multiple chimaeric animals, each carrying a mix of donor and host germ cells in their gonads. However, such chimaeric germlines would produce offspring from both donor and host genotypes, limiting the rate of genetic improvement. To resolve this problem, we disrupted the RNA‐binding protein DAZL and generated germ cell‐deficient host animals. Using Cas9‐mediated homology‐directed repair (HDR), we introduced a DAZL loss‐of‐function mutation in male ovine fetal fibroblasts. Following manual single cell isolation, 4/48 (8.3%) of donor cell strains were homozygously HDR‐edited. Sequence‐validated strains were used as nuclear donors for somatic cell cloning to generate three lambs, which died at birth. All DAZL null male neonatal sheep lacked germ cells on histological sections and showed greatly reduced germ cell markers. Somatic cells within their testes were morphologically intact and expressed normal levels of lineage‐specific markers, suggesting that the germ cell niche remained intact. This extends the DAZL mutant phenotype beyond mice into agriculturally relevant ruminants, providing a pathway for using absolute germline transmitters in rapid livestock improvement.

History

Rights statement

© 2020 Wiley Periodicals LLC.

Publication date

2020-11-29

Project number

  • Non revenue

Language

  • English

Does this contain Māori information or data?

  • No

Publisher

Wiley

Journal title

Molecular Reproduction and Development

ISSN

1040-452X

Citation

McLean, Z. L., Appleby, S. J., Wei, J., Snell, R. G., & Oback, B. (2021). Testes of DAZL null neonatal sheep lack prospermatogonia but maintain normal somatic cell morphology and marker expression. Molecular Reproduction and Development, 88(12), 3–14. doi:10.1002/mrd.23443

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