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Lack of Association of a Spontaneous Mutation of the Chrm2 Gene with Behavioral and Physiologic Phenotypic Differences in Inbred Mice

机译:缺乏自发小鼠Chrm2基因的自发突变与行为和生理表型差异的关联。

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摘要

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.
机译:Chrm2基因中的核苷酸取代C797T导致亮氨酸被CHRM2蛋白的266位(P266L)脯氨酸取代。因为Chrm2编码2型毒蕈碱受体,所以这种突变可能影响小鼠的生理和行为表型。在具有(BALB / cByJ)或没有(C57BL / 6J)突变的小鼠品系中,Chrm2 mRNA在具有高胆碱能神经支配的2个大脑区域中没有差异表达。另外,在Chrm2中具有和不具有C797T点突变的小鼠品系在毒蕈碱结合特性方面没有显着差异。在听觉惊吓,预脉冲抑制和毒蕈碱激动剂oxotremorine的生理效应方面检测到了菌株间的差异。但是,这些措施中的株间差异与突变的存在无关。尽管我们无法将可测量的表型与Chrm2突变相关联,但在其他遗传背景下或在其他性状的背景下对该突变进行评估可能会显示出不同的影响。因此,尽管我们的研究结果是负面的,但在比较具有Chrm2基因不同等位基因的小鼠时,应谨慎评估涉及毒蕈碱功能的特征。

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