Functional analysis of the SRY–KRAB interaction in mouse sex determination

Polanco, Juan Carlos, Wilhelm, Dagmar, Mizusaki, Hirofumi, Jackson, Andrew, Browne, Catherine, Davidson, Tara, Harley, Vincent, Sinclair, Andrew and Koopman, Peter (2009) Functional analysis of the SRY–KRAB interaction in mouse sex determination. Biology of The Cell, 101 1: 55-67. doi:10.1042/BC20080061

Author Polanco, Juan Carlos
Wilhelm, Dagmar
Mizusaki, Hirofumi
Jackson, Andrew
Browne, Catherine
Davidson, Tara
Harley, Vincent
Sinclair, Andrew
Koopman, Peter
Title Functional analysis of the SRY–KRAB interaction in mouse sex determination
Journal name Biology of The Cell   Check publisher's open access policy
ISSN 0248-4900
Publication date 2009-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1042/BC20080061
Open Access Status
Volume 101
Issue 1
Start page 55
End page 67
Total pages 12
Place of publication London, England
Publisher Portland Press Ltd
Language eng
Subject 970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
Formatted abstract
Background information. SRY (sex-determining region Y), the master regulator of male development in mammals, has been studied extensively for more than 17 years, but how the SRY protein triggers the chain of events leading to testis development remains unclear. SRY probably requires a partner protein to elicit its molecular function. KRAB-O, a novel protein containing a KRAB (Krüppel-associated box) domain only, was suggested recently as a candidate SRY partner. In order to investigate the possible role of KRAB-O in sex determination, we studied its expression and conducted functional assays of the SRY–KRAB interaction.

Results. More than 100 KRAB genes were found to be expressed in mouse developing gonads, including 19 transcripts encoded by the KRAB-O cluster that were found to be expressed in somatic cells at 11.5 dpc (days post-coitum). Loss-of-function analysis in Sry-expressing cultured cells, using shRNA (small hairpin RNA) constructs directed against KRAB-O and its homologous genes, resulted in a reduced ability to up-regulate Sox9 [SRY-related HMG (high-mobility group)-box 9]; however, KRAB-knockdown mice exhibited normal testis development.

Conclusions. Reduced Sox9 expression in KRAB-knockdown cells supports a role for KRAB-O and perhaps other KRAB genes in mediating SRY function. Overlapping expression and potential redundancy between members of the large KRAB-O gene cluster may mask any loss-of-function in vivo, presenting clear challenges for further functional analysis.
Keyword sex determination
sex-determining region Y (SRY)
Krüppel-associated box (KRAB)
molecular mechanism
testis development
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Published as Immediate Publication 30 June 2008

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Created: Tue, 03 Feb 2009, 02:24:09 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience