The A529T polymorphism in the CHRNA4 gene has been shown to influence varying responses to nicotine and it was found that mice strains with the A529T genotype consumed less nicotine (in solution) and preferred solutions with a lower concentration of nicotine (Butt et al. 2005; Stitzel et al. 2000; Tritto et al. 2002). Wilking and others found that CHRNA4 A529T knock-in mice exhibited greater sensitivity to the hypothermic effects of nicotine, consumed less nicotine, and did not develop conditioned place preference. A529T mice produced a smaller maximal functional response to acetylcholine (ACh) than T529A littermates and the percent of response to ACh by high sensitivity α4* nAChRs was significantly greater for nAChRs containing the A529T variant (Wilking et al. 2010).
