Document Detail

Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development.
MedLine Citation:
PMID:  10571183     Owner:  NLM     Status:  MEDLINE    
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.
N A Arango; R Lovell-Badge; R R Behringer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell     Volume:  99     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-14     Completed Date:  1999-12-14     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  409-19     Citation Subset:  IM    
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MeSH Terms
Anti-Mullerian Hormone
Binding Sites
DNA-Binding Proteins / metabolism*
Fushi Tarazu Transcription Factors
Gene Targeting
Growth Inhibitors / genetics*,  physiology
High Mobility Group Proteins / metabolism*
Homeodomain Proteins
Mice, Inbred C57BL
Mice, Transgenic
Mullerian Ducts / physiology
Promoter Regions, Genetic*
Receptors, Cytoplasmic and Nuclear
SOX9 Transcription Factor
Sexual Maturation / physiology*
Steroidogenic Factor 1
Testicular Hormones / genetics*,  physiology
Transcription Factors / metabolism*
Transcription, Genetic
Grant Support
CA09299/CA/NCI NIH HHS; HD30284/HD/NICHD NIH HHS; MC_U117562207//Medical Research Council
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Fushi Tarazu Transcription Factors; 0/Glycoproteins; 0/Growth Inhibitors; 0/High Mobility Group Proteins; 0/Homeodomain Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/SOX9 Transcription Factor; 0/Sox9 protein, mouse; 0/Steroidogenic Factor 1; 0/Testicular Hormones; 0/Transcription Factors; 0/steroidogenic factor 1, mouse; 80497-65-0/Anti-Mullerian Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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