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 encoded by an immediate-early serum response gene expressed in various physiological 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 were 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 decreased GH content observed in these animals; in contrast gonadotropes are normal in number, but specifically fail to synthesize the beta-subunit of LH. In the ovary, LH receptor expression is prevented, indicating an involvement of Krox-24 at two levels at least of the pituitary-gonadal axis. Our data, together with the results of a previous report describing another Krox-24 mutant allele, suggest that Krox-24 may have two distinct molecular functions in the anterior pituitary: transcriptional activation of the LHbeta gene in gonadotropes and control of cell proliferation and/or survival in somatotropes by unknown mechanisms.
Topilko
P
P
U-368, INSERM, Biologie Moléculaire du Développement, Ecole Normale Supérieure, Paris, France.
Schneider-Maunoury
S
S
Levi
G
G
Trembleau
A
A
Gourdji
D
D
Driancourt
M A
MA
Rao
C V
CV
Charnay
P
P
D000818:Animals; D001824:Body Constitution / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005836:Genitalia, Female / Q000254:growth & development; D005837:Genitalia, Male / Q000254:growth & development; D013006:Growth Hormone / Q000096:biosynthesis; D006720:Homozygote; D017874:Immediate-Early Proteins; D007246:Infertility / Q000235:genetics; D007986:Luteinizing Hormone / Q000008:administration & dosage / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000002:abnormalities* / Q000254:growth & development / Q000473:pathology; D010641:Phenotype; D010903:Pituitary Gland, Anterior / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D007986:Luteinizing Hormone; D013006:Growth Hormone