MULTIPLE PITUITARY AND OVARIAN DEFECTS IN KROX-24 (NGFI-A, EGR-1)-TARGETED MICE

The zinc finger transcription factor Krox-24 (NGFI-A, Egr-1) is encode d by an immediate-early serum response gene expressed in various physi ological situations and tissues. To investigate its function, we have created a null allele. Mice homozygous for the mutation have a reduced body size, and both males and females are sterile. These phenotypes w ere related to defects in the anterior pituitary of both sexes and in the ovary. In the pituitary, two cell lineages expressing Krox-24 are differentially affected by the mutation: somatotropes present abnormal cytological features and are reduced in number, consistent with the d ecreased GH content observed in these animals; in contrast gonadotrope s are normal in number, but specifically fail to synthesize the beta-s ubunit of LH. In the ovary, LH receptor expression is prevented, indic ating an involvement of Krox-24 at two levels at least of the pituitar y-gonadal axis. Our data, together with the results of a previous repo rt describing another Krox-24 mutant allele, suggest that Krox-24 may have two distinct molecular functions in the anterior pituitary: trans criptional activation of the LH beta gene in gonadotropes and control of cell proliferation and/or survival in somatotropes by unknown mecha nisms.