Hypomorphic phenotype in mice with pituitary-specific knockout of steroidogenic factor 1

The bacteriophage Cre recombinase provides a powerful approach for tissue-s pecific gene inactivation. Using a Cre transgene driven by the common alpha subunit of glycoprotein hormones alpha GSU-Cre), we have previously inacti vated steroidogenic factor 1 (SF-1) in the anterior pituitary, causing hypo gonadotropic hypogonadism with sexual infantilism, sterility, and severe go nadal hypoplasia, We now explore the molecular mechanisms underlying a hypo morphic gonadal phenotype in mice carrying two flexed SF-l alleles (F/F) re lative to mice carrying one recombined and one flexed allele (F/R). Because their ore-mediated disruption of the locus encoding SF-1 was less efficien t, (alpha GSU-Cre, F/F mice retained some gonadotropin-expressing cells in the anterior pituitary, thereby stimulating some gonadal function. This nov el in vivo model for exploring the effects of differing levels of gonadotro pins on gonadal development highlights the need for careful genotype-phenot ype comparisons in studies using ore recombinase to produce tissue-specific knockouts. (C) 2001 Wiley-Liss, Inc.