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• W2916091908 endingPage "372" @default.
• W2916091908 startingPage "357" @default.
• W2916091908 abstract "GATA4 is a transcription factor essential for male sex determination, testicular differentiation during fetal development, and male fertility in the adult. GATA4 exerts part of its function by regulating multiple genes in the steroidogenic enzyme pathway. In spite of these crucial roles, how the activity of this factor is regulated remains unclear.Studies in gonadal cell lines have shown that GATA4 is phosphorylated on at least two serine residues-serine 105 (S105) and serine 261 (S261)-and that this phosphorylation is important for GATA4 activity. The objective of the present study is to characterize the endogenous role of GATA4 S105 and S261 phosphorylation in the mouse testis.We examined both previously described GATA4 S105A mice and a novel GATA4 S261A knock-in mouse that we generated by CRISPR/Cas9 gene editing. The male phenotype of the mutants was characterized by assessing androgen-dependent organ weights, hormonal profiles, and expression of multiple testicular target genes using standard biochemical and molecular biology techniques.The fecundity of crosses between GATA4 S105A mice was reduced but without a change in sex ratio. The weight of androgen-dependent organs was smaller when compared to wild-type controls. Plasma testosterone levels showed a 70% decrease in adult GATA4 S105A males. This decrease was associated with a reduction in Cyp11a1, Cyp17a1, and Hsd17b3 expression. GATA4 S261A mice were viable and testis morphology appeared normal. Testosterone production and steroidogenic enzyme expression were not altered in GATA4 S261A males.Our analysis showed that blocking GATA4 S105 phosphorylation is associated with decreased androgen production in males. In contrast, S261 phosphorylation by itself is dispensable for GATA4 function. These results confirm that endogenous GATA4 action is essential for normal steroid production in males and that this activity requires phosphorylation on at least one serine residue." @default.
• W2916091908 created "2019-03-02" @default.
• W2916091908 creator A5014336180 @default.
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• W2916091908 date "2019-02-22" @default.
• W2916091908 modified "2023-10-02" @default.
• W2916091908 title "Phosphorylation of<scp>GATA</scp>4 serine 105 but not serine 261 is required for testosterone production in the male mouse" @default.
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• W2916091908 doi "https://doi.org/10.1111/andr.12601" @default.
• W2916091908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30793514" @default.
• W2916091908 hasPublicationYear "2019" @default.
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