title: 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.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arnold
authors.forename: Jeremy
authors.initials: J
authors.lastname: Turner
authors.forename: Vickram
authors.initials: V
authors.lastname: Ramkumar
authors.forename: Larry F
authors.initials: LF
authors.lastname: Hughes
authors.forename: Rita A
authors.initials: RA
authors.lastname: Trammell
authors.forename: Linda A
authors.initials: LA
authors.lastname: Toth
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology*; D001667:Binding, Competitive / Q000235:genetics; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010095:Oxotremorine / Q000494:pharmacology; D010641:Phenotype; D043585:Receptor, Muscarinic M2 / Q000235:genetics* / Q000378:metabolism; D013216:Reflex, Startle / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012472:Salivation / Q000187:drug effects; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014202:Tremor / Q000139:chemically induced
chemical_list: D017931:DNA Primers; D043585:Receptor, Muscarinic M2; D010095:Oxotremorine
references.citation: J Comp Neurol. 1993 Mar 22;329(4):438-57
references.pmid: 8454735
references.citation: J Acoust Soc Am. 1983 May;73(5):1686-93
references.pmid: 6615589
references.citation: Chronobiol Int. 2004 Mar;21(2):229-37
references.pmid: 15332344
references.citation: Am J Med Genet. 2002 Jul 8;114(5):527-9
references.pmid: 12116189
references.citation: Physiol Res. 2004;53 Suppl 1:S131-40
references.pmid: 15119944
references.citation: Genes Brain Behav. 2006 Jul;5(5):423-31
references.pmid: 16879636
references.citation: Genes Brain Behav. 2008 Mar;7(2):173-83
references.pmid: 17696998
references.citation: Hum Mol Genet. 2009 Apr 15;18(8):1504-9
references.pmid: 19181679
references.citation: J Neurophysiol. 1998 May;79(5):2603-14
references.pmid: 9582232
references.citation: J Comp Neurol. 1995 Jan 16;351(3):339-56
references.pmid: 7706546
references.citation: Br J Pharmacol. 2005 Feb;144(4):566-75
references.pmid: 15655507
references.citation: J Interferon Cytokine Res. 1996 Dec;16(12):1065-72
references.pmid: 8974010
references.citation: Psychopharmacology (Berl). 1997 Jul;132(2):169-80
references.pmid: 9266614
references.citation: Ann N Y Acad Sci. 1999 Jun 29;877:202-16
references.pmid: 10415651
references.citation: Behav Brain Res. 2000 Nov;115(2):117-41
references.pmid: 11000416
references.citation: Behav Genet. 1999 Sep;29(5):339-48
references.pmid: 10765562
references.citation: J Auton Pharmacol. 1999 Apr;19(2):77-84
references.pmid: 10466939
references.citation: Eur J Neurosci. 2006 Jun;23(12):3245-58
references.pmid: 16820015
references.citation: Science. 1998 Dec 18;282(5397):2258-61
references.pmid: 9856949
references.citation: Pneumonol Alergol Pol. 2009;77(1):5-10
references.pmid: 19308904
references.citation: Genome Res. 2004 Sep;14(9):1806-11
references.pmid: 15342563
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:423-50
references.pmid: 14744253
references.citation: Behav Genet. 2006 Sep;36(5):627-39
references.pmid: 16823639
references.citation: Proc Am Thorac Soc. 2005;2(4):305-10; discussion 311-2
references.pmid: 16267353
references.citation: Hear Res. 1998 Jan;115(1-2):162-74
references.pmid: 9472745
references.citation: J Neuroimmunol. 1995 Apr;58(1):89-99
references.pmid: 7730450
references.citation: Behav Neurosci. 2003 Aug;117(4):716-27
references.pmid: 12931957
references.citation: J Neurosci. 1994 Mar;14(3 Pt 1):1176-94
references.pmid: 8120618
references.citation: FEBS Lett. 2006 Jan 9;580(1):23-6
references.pmid: 16364317
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):684-690
references.pmid: 19644963
references.citation: J Clin Invest. 1998 Jul 1;102(1):242-8
references.pmid: 9649578
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3633-8
references.pmid: 19211801
references.citation: Ann Med. 2009;41(3):197-207
references.pmid: 18979273
references.citation: Eur J Neurosci. 2006 Oct;24(7):1967-75
references.pmid: 17040474
references.citation: J Assoc Res Otolaryngol. 2007 Dec;8(4):539-50
references.pmid: 17952509
references.citation: J Pharmacol Exp Ther. 2006 Jan;316(1):279-88
references.pmid: 16188951
references.citation: Pharmacol Rev. 2002 Jun;54(2):323-74
references.pmid: 12037145
references.citation: Respir Physiol Neurobiol. 2008 May 31;161(3):223-9
references.pmid: 18440286