title: G(z alpha) deficient mice: enzyme levels in the autonomic nervous system, neuronal survival and effect of genetic background.
abstract: Our laboratory has generated a genetically mutant mouse in which the alpha subunit of the heterotrimeric GTP binding protein, G(z) has been made dysfunctional by homologous recombination to determine its in vivo function. These animals show a characteristic failure to thrive phenotype. G(z alpha) is expressed in a variety of nervous system tissues as well as in the adrenal medulla. We therefore examined the autonomic nervous system of the G(z alpha) deficient mouse by measuring the activity of tyrosine hydroxylase and choline acetyltransferase in the superior cervical ganglia, submaxillary gland and the adrenal medulla. Preliminary results using animals of mixed BALB/c and C57BL/6 strains gave inconsistent results. Further experiments demonstrated differences in the activity of tyrosine hydroxylase and choline acetyltransferase between BALB/c and C57BL/6 mouse strains. The analysis of the pure strains showed a reduction in the size and enzyme levels of the adrenal gland and submaxillary glands of the G(z alpha) deficient mouse suggesting a role for adrenal insufficiency and/or nutritional disorders for the failure to thrive phenotype. The survival of sympathetic and sensory neurons was also examined in the G(z alpha) deficient mouse and in the presence of pertussis toxin, sympathetic but not sensory neuronal survival in G(z alpha) deficient mice was significantly attenuated. This suggests that in vivo other pertussis toxin sensitive G proteins may be recruited to compensate for the loss of G(z alpha).
authors: Developmental Neurobiology Group, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Box 334, Canberra, ACT 2601, Australia.
authors: Kim L
authors: KL
authors: Powell
authors: Klaus I
authors: KI
authors: Matthaei
authors: Katharina
authors: K
authors: Heydon
authors: Ian A
authors: IA
authors: Hendry
mesh_terms: D000313:Adrenal Medulla / Q000201:enzymology / Q000254:growth & development / Q000294:innervation; D000375:Aging / Q000378:metabolism; D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D001342:Autonomic Nervous System Diseases / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009475:Neurons, Afferent / Q000166:cytology / Q000201:enzymology; D037342:Pertussis Toxin; D013363:Submandibular Gland / Q000201:enzymology / Q000254:growth & development / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse; D010566:Virulence Factors, Bordetella; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins