Pituitary-specific Gata2 knockout: effects on gonadotrope and thyrotrope function.
GATA2 is expressed in the pituitary during development and in adult gonadotropes and thyrotropes. It is proposed to be important for gonadotrope and thyrotrope cell fate choice and for TSH production. To test this idea, we produced a pituitary-specific knockout of Gata2, designed so that the DNA-binding zinc-finger region is deleted in the presence of a pituitary-specific recombinase transgene. These mice have reduced secretion of gonadotropins basally and in response to castration challenge, although the mice are fertile. GATA2 deficiency also compromises thyrotrope function. Mutants have fewer thyrotrope cells at birth, male Gata2-deficient mice exhibit growth delay from 3-9 wk of age, and adult mutants produce less TSH in response to severe hypothyroidism after radiothyroidectomy. Therefore, Gata2 appears to be dispensable for gonadotrope and thyrotrope cell fate and maintenance, but important for optimal gonadotrope and thyrotrope function. Gata2-deficient mice exhibit elevated levels of Gata3 transcripts in the pituitary gland, suggesting that GATA3 can compensate for GATA2.
Charles
Michael A
MA
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0618, USA.
Saunders
Thomas L
TL
Wood
William M
WM
Owens
Kailey
K
Parlow
A F
AF
Camper
Sally A
SA
Ridgway
E C
EC
Gordon
David F
DF
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D001835:Body Weight; D004247:DNA / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D050989:GATA2 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000235:genetics; D006065:Gonadotropins, Pituitary / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009919:Orchiectomy; D010902:Pituitary Gland / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D013965:Thyroidectomy; D013972:Thyrotropin / Q000096:biosynthesis; D014158:Transcription, Genetic
D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D006065:Gonadotropins, Pituitary; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D004247:DNA