Dwarf mice produced by genetic ablation of growth hormone-expressing cells.
Fusion of the 310 bp located 5' of the rat growth hormone (GH) gene to the human GH structural gene resulted in somatotrope-specific expression in transgenic mice. Human GH transcripts were detected only in pituitaries of these mice, and immunocytochemical analyses revealed that this expression was limited to GH-expressing cell types. The rat GH 5' sequences were then used to direct the expression of diphtheria toxin to the GH-expressing cells of transgenic mice. A line of mice was established which lacks detectable levels of circulating GH. This deficiency resulted in dwarfism; transgenic animals grew only to half the size of nontransgenic littermates. Nearly all somatotropes were absent, as shown by GH immunostaining in the transgenic pituitaries. Prolactin (PRL)-producing lactotropes, thought to share a common cellular origin with somatotropes, were also reduced in numbers. A model for the lineal relationships between GH- and PRL-synthesizing cells is proposed.
Behringer
R R
RR
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Mathews
L S
LS
Palmiter
R D
RD
Brinster
R L
RL
D000818:Animals; D003001:Cloning, Molecular; D004167:Diphtheria Toxin / Q000235:genetics; D004392:Dwarfism / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D008954:Models, Biological; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D013234:Stem Cells
D004167:Diphtheria Toxin; D011388:Prolactin; D013006:Growth Hormone