PMID- 10571183 OWN - NLM STAT- MEDLINE DCOM- 19991214 LR - 20220129 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 99 IP - 4 DP - 1999 Nov 12 TI - Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. PG - 409-19 AB - Mutations were introduced into conserved steroidogenic factor 1 (SF1)- and SOX9-binding sites within the endogenous mouse Mullerian inhibiting substance (Mis) promoter. Male mice homozygous for the mutant SF1-binding site correctly initiated Mis transcription in fetal testes, although at significantly reduced levels. Surprisingly, sufficient MIS was produced to eliminate the MUllerian ducts. In contrast, males homozygous for the mutant SOX9-binding site did not initiate Mis transcription, resulting in pseudohermaphrodites. These studies suggest an essential role for SOX9 in the initiation of Mis transcription, whereas SF1 appears to act as a quantitative regulator of Mis transcript levels, perhaps for influencing non-Mullerian duct tissues. Comparative studies of Mis expression in vertebrates indicate that the Mis promoter receives transcriptional inputs that vary between species but result in the same functional readout. FAU - Arango, N A AU - Arango NA AD - Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. FAU - Lovell-Badge, R AU - Lovell-Badge R FAU - Behringer, R R AU - Behringer RR LA - eng GR - MC_U117562207/MRC_/Medical Research Council/United Kingdom GR - HD30284/HD/NICHD NIH HHS/United States GR - CA09299/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DNA-Binding Proteins) RN - 0 (Fushi Tarazu Transcription Factors) RN - 0 (Glycoproteins) RN - 0 (Growth Inhibitors) RN - 0 (High Mobility Group Proteins) RN - 0 (Homeodomain Proteins) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (SOX9 Transcription Factor) RN - 0 (Sox9 protein, mouse) RN - 0 (Steroidogenic Factor 1) RN - 0 (Testicular Hormones) RN - 0 (Transcription Factors) RN - 0 (steroidogenic factor 1, mouse) RN - 80497-65-0 (Anti-Mullerian Hormone) SB - IM MH - Animals MH - Anti-Mullerian Hormone MH - Binding Sites MH - DNA-Binding Proteins/*metabolism MH - Female MH - Fushi Tarazu Transcription Factors MH - Gene Targeting MH - *Glycoproteins MH - Growth Inhibitors/*genetics/physiology MH - High Mobility Group Proteins/*metabolism MH - Homeodomain Proteins MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Mullerian Ducts/physiology MH - Mutagenesis MH - *Promoter Regions, Genetic MH - Receptors, Cytoplasmic and Nuclear MH - SOX9 Transcription Factor MH - Sexual Maturation/*physiology MH - Steroidogenic Factor 1 MH - Testicular Hormones/*genetics/physiology MH - Transcription Factors/*metabolism MH - Transcription, Genetic MH - Up-Regulation EDAT- 1999/11/26 00:00 MHDA- 1999/11/26 00:01 CRDT- 1999/11/26 00:00 PHST- 1999/11/26 00:00 [pubmed] PHST- 1999/11/26 00:01 [medline] PHST- 1999/11/26 00:00 [entrez] AID - S0092-8674(00)81527-5 [pii] AID - 10.1016/s0092-8674(00)81527-5 [doi] PST - ppublish SO - Cell. 1999 Nov 12;99(4):409-19. doi: 10.1016/s0092-8674(00)81527-5.