Sox genes encode proteins related to each other, and to the sex determining
gene Sry, by the presence of a DNA binding motif known as the HMG domain.
Although HMG domains can bind to related DNA sequences, Sox gene products m
ay achieve target gene specificity by binding to preferred target sequences
or by interacting with specific partner proteins. To assess their function
al similarities, we replaced the HMG box of Sry with the HMG box of Sox3 or
Sox9 and tested whether these constructs caused sex reversal in XX mice. O
ur results indicate that such chimeric transgenes can functionally replace
Sry and elicit development of testis cords, male patterns of gene expressio
n, and elaboration of male secondary sexual characteristics. This implies t
hat chimeric SRY proteins with SOX HMG domains can bind to and regulate SRY
target genes and that potential SRY partner factor interactions are not di
srupted by HMG domain substitutions. (C) 2000 Wiley-Liss, Inc.