TY - JOUR
T1 - Targeted mutagenesis of the endogenous mouse Mis gene promoter
T2 - In vivo definition of genetic pathways of vertebrate sexual development
AU - Arango, Nelson A.
AU - Lovell-Badge, Robin
AU - Behringer, Richard R.
N1 - Funding Information:
We thank Sara Morais da Silva and Ryohei Sekido for communicating unpublished information; David Anderson for the CMV-cre (C57BL/6) transgenic mouse line; Andras Nagy for ploxPneo-1; Steve O'Gorman for pOG231; Soazik Jamin, Sophia Tsai, and Deanne Whitworth for helpful comments on the manuscript; and Blanche Capel for discussions. These studies were supported by a grant from the National Institutes of Health (HD30284) to R. R. B.; R. L.-B. is grateful for support from the UK Medical Research Council and the Louis Jeantet Foundation. N. A. A. was supported by the National Science Foundation Developmental Biology Training Grant BIR-9413237 and the National Institutes of Health Molecular Genetics of Cancer Training Grant (CA09299).
PY - 1999
Y1 - 1999
N2 - 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.
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.
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U2 - 10.1016/S0092-8674(00)81527-5
DO - 10.1016/S0092-8674(00)81527-5
M3 - Article
C2 - 10571183
AN - SCOPUS:0032705186
SN - 0092-8674
VL - 99
SP - 409
EP - 419
JO - Cell
JF - Cell
IS - 4
ER -