TSSK3, a novel target for male contraception, is required for spermiogenesis.
TSSK3
evolution
fertilization
intronless gene
kinases
nonhormonal male contraceptive
sperm
spermatogenesis
testis-specific
Journal
Molecular reproduction and development
ISSN: 1098-2795
Titre abrégé: Mol Reprod Dev
Pays: United States
ID NLM: 8903333
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
26
08
2021
accepted:
24
09
2021
pubmed:
9
10
2021
medline:
5
4
2022
entrez:
8
10
2021
Statut:
ppublish
Résumé
We have previously shown that members of the family of testis-specific serine/threonine kinases (TSSKs) are post-meiotically expressed in testicular germ cells and in mature sperm in mammals. The restricted post-meiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggest that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the TSSK6 knock-out (KO) mice and of the double TSSK1/TSSK2 KO. The aim of this study was to develop KO mouse models of TSSK3 and to validate this kinase as a target for the development of a male contraceptive. We used CRISPR/Cas9 technology to generate the TSSK3 KO allele on B6D2F1 background mice. Male heterozygous pups were used to establish three independent TSSK3 KO lines. After natural mating of TSSK3 KO males, females that presented a plug (indicative of mating) were monitored for the following 24 days and no pregnancies or pups were found. Sperm numbers were drastically reduced in all three KO lines and, remarkably, round spermatids were detected in the cauda epididymis of KO mice. From the small population of sperm recovered, severe morphology defects were detected. Our results indicate an essential role of TSSK3 in spermiogenesis and support this kinase as a suitable candidate for the development of novel nonhormonal male contraceptives.
Identifiants
pubmed: 34623009
doi: 10.1002/mrd.23539
pmc: PMC8961454
mid: NIHMS1746392
doi:
Substances chimiques
Protein Serine-Threonine Kinases
EC 2.7.11.1
TSSK3 protein, human
EC 2.7.11.1
Tssk2 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
718-730Subventions
Organisme : NICHD NIH HHS
ID : R03 HD101762
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD093540
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM108556
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD093540
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM135096
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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