Gzalpha deficient mice: enzyme levels in the autonomic nervous system, neuronal survival and effect of genetic background

Date

2002

Authors

Powell, Kim
Matthaei, Klaus
Heydon, Katharina
Hendry, Ian

Journal Title

Journal ISSN

Volume Title

Publisher

Pergamon-Elsevier Ltd

Abstract

Our laboratory has generated a genetically mutant mouse in which the alpha subunit of the heterotrimeric GTP binding protein, Gz has been made dysfunctional by homologous recombination to determine its in vivo function. These animals show a characteristic failure to thrive phenotype. Gzα 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 Gzα 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 Gzα 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 Gzα deficient mouse and in the presence of pertussis toxin, sympathetic but not sensory neuronal survival in Gzα 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 Gzα.

Description

Keywords

Keywords: brain enzyme; choline acetyltransferase; guanine nucleotide binding protein; pertussis toxin; tyrosine 3 monooxygenase; adrenal insufficiency; adrenal medulla; animal cell; animal experiment; animal tissue; article; autonomic nervous system; cell survival G protein; Genetically mutant mouse; Strain differences

Citation

Source

International Journal of Developmental Neuroscience

Type

Journal article

Book Title

Entity type

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DOI

10.1016/S0736-5748(02)00002-3

Restricted until

2037-12-31