Lack of Association of a Spontaneous Mutation of the Chrm2 Gene with Behavioral and Physiologic Phenotypic Differences in Inbred Mice
Abstract:The nucleotide substitution C797T in the Chrm2 gene causes substitution of leucine for proline at position 266 (P266L) of the CHRM2 protein. Because Chrm2 codes for the type 2 muscarinic receptor, this mutation could influence physiologic and behavioral phenotypes of mice. Chrm2 mRNA was not differentially expressed in 2 brain regions with high cholinergic innervation in a mouse strain that does (BALB/cByJ) or does not (C57BL/6J) have the mutation. In addition, strains of mice with and without the C797T point mutation in Chrm2 did not differ significantly in muscarinic binding properties. Variation across strains was detected in terms of acoustic startle, prepulse inhibition, and the physiologic effects of the muscarinic agonist oxotremorine. However, interstrain differences in these measures did not correlate with the presence of the mutation. Although we were unable to associate a measurable phenotype with the Chrm2 mutation, assessment of the mutation on other genetic backgrounds or in the context of other traits might reveal differential effects. Therefore, despite our negative findings, evaluation of characteristics that involve muscarinic function should be undertaken with caution when comparing mice with different alleles of the Chrm2 gene.
Document Type: Research Article
Affiliations: 1: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 2: Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, Department of Psychology, Illinois College Jacksonville, Illinois 3: Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois 4: Department of Medicine, Southern Illinois University School of Medicine, Springfield, Illinois 5: Departments of Pharmacology, Surgery, Southern Illinois University School of Medicine, Springfield, Illinois; Email: email@example.com
Publication date: August 1, 2010
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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