DNA regulatory sequences of the rat tyrosine hydroxylase gene direct correct catecholaminergic cell-type specificity of a human growth hormone reporter in the CNS of transgenic mice causing a dwarf phenotype.
Transgenic mice bearing 4.8 kilobases (kb) of upstream rat tyrosine hydroxylase (TH) sequences linked to a human growth hormone gene (hGH) exhibited cell-specific expression of hGH in all the appropriate catecholaminergic neurons in the central nervous system (CNS), although with different penetrance in two different mouse lineages. No ectopic expression was observed in any brain or peripheral region in one founder and its progeny. In another founder there was some ectopic expression in addition to appropriate and high levels of tissue-specific expression in all catecholaminergic areas. These results identify regulatory sequences that are sufficient for targeting expression to all catecholaminergic CNS neurons. Also, expression of exogenous hGH in the hypothalamus caused a dwarf phenotype, generating a novel genetic model for GH deficiency of hypothalamic origin.
Department of Microbiology, Tufts University School of Medicine, Boston, MA 02111.
S A
SA
Banerjee
S
S
Roffler-Tarlov
M
M
Szabo
L
L
Frohman
D M
DM
Chikaraishi
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D004392:Dwarfism / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012727:Sex Characteristics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D002395:Catecholamines; D013006:Growth Hormone; D014446:Tyrosine 3-Monooxygenase