The Ames dwarf gene is required for Pit-1 gene activation.
The tissue-specific POU domain transcription factor Pit-1 is required for phenotypic specification of three cell types in the anterior pituitary gland of mammals: somatotropes, thyrotropes, and lactotropes. Mutations in the Pit-1 gene, as first described in Snell and Jackson dwarf (dw) mice, led to pituitary hypoplasia due to lack of these three cell types, as well as hypothyroidism and dwarfism because of deficiency of thyroid-stimulating hormone and growth hormone, respectively. The Ames dwarf (df) exhibits a phenotype identical to that of Pit-1 mutated mice but the defective gene has been mapped to a locus on mouse chromosome 11, distinct from the Pit-1 gene located on mouse chromosome 6. Our studies indicate that initial activation of the Pit-1 gene is deficient in the Ames dwarf. This suggests that the df gene is required for activation of the Pit-1 gene and provides evidence for a hierarchy of tissue-specific factors required for cellular commitment in the anterior pituitary gland.
Andersen
B
B
Howard Hughes Medical Institute, School and Department of Medicine, University of California, San Diego, La Jolla 92093-0648, USA.
Pearse
R V
RV
Jenne
K
K
Sornson
M
M
Lin
S C
SC
Bartke
A
A
Rosenfeld
M G
MG
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010902:Pituitary Gland / Q000196:embryology*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse