Combined haploinsufficiency of SF-1 and GATA4 does not reveal a genetic interaction in mouse gonadal development.
The nuclear receptor steroidogenic factor 1 (SF-1 or NR5A1) and the zinc finger protein GATA4 mediate key events in the early steps of gonadal development and sex differentiation, presumably by activating the expression of essential target genes. An important SF-1 target in male sex differentiation is the gene encoding the anti-Müllerian hormone (AMH), which induces regression of the Müllerian ducts in the developing male embryo. In cell transfection studies, there is apparent cooperation between GATA4 and SF-1 in the regulation of both human and mouse Amh promoters. We hypothesized that compound haploinsufficiency of both SF-1 and GATA4, by reducing their synergism, might cause a more severe phenotype than that seen in mice that were heterozygous for either SF-1 or Gata4 alone. Surprisingly, in adult and embryonic mice, compound haploinsufficiency of SF-1 and GATA4 caused no gonadal or reproductive abnormalities beyond those seen in SF-1(+/-) mice. Thus, although cooperation between SF-1 and GATA4 very likely is important for regulation of their target genes, such synergy was not revealed in our in vivo studies of gonadal development and function.
Pelusi
C
C
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Tex. 75390, USA.
Zhao
L
L
Stallings
N R
NR
Parker
K L
KL
D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D006238:Haploidy; D006579:Heterozygote; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010053:Ovary / Q000166:cytology / Q000196:embryology*; D012733:Sex Differentiation; D054339:Steroidogenic Factor 1 / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000196:embryology*
D050991:GATA4 Transcription Factor; D054339:Steroidogenic Factor 1; D054304:Anti-Mullerian Hormone