多巴胺 D1、D3受体敲除及双基因敲除对小鼠体重的影响

摘要

目的：研究多巴胺受体介导的神经及生理活动。方法引进多巴胺D1和D3受体敲除小鼠，繁育出多巴胺D1 D3受体双敲除小鼠。选择D1受体敲除、D3受体敲除、D1 D3双基因敲除与WT四种基因型雄鼠各7只，对其30 d、50 d、70 d小鼠24 h内的进食量、饮水量及体重进行测量，探讨多巴胺D1受体、D3受体敲除小鼠及D1 D3受体双基因敲除小鼠与野生型进食、饮水、体重增长的比较。结果多巴胺D1、D3受体基因对小鼠21 d和35 d的体重增长有一个较为显著的影响，直到90 d时，各基因型小鼠体重间无统计学差异。结论多巴胺可能通过调节HPA轴的活性，从而调控仔鼠的觅食与饱腹感，最终影响仔鼠初生重及泌乳期体重。同时，多巴胺D1、D3受体基因的敲除可能通过干扰泌乳等母性行为而影响小鼠的体重。研究结果为利用基因敲除小鼠研究多巴胺D1、D3受体的功能及它们之间的相互作用奠定坚实的基础。%Objective To study the effect of dopamine receptors on neurological and physiological activities. Methods Dopamine D1 receptor gene (DRD1) knockout mice and dopamine D3 receptor (DRD3) gene knockout mice were introduced, and double gene knockout mice were bred in our lab.Seven SPF male mice in each group were used in this experiment.The food intake, water intake, body weight gain for 24 hours were tested on the age of 30 d, 50 d, and 70 d and were compared with those of wild type mice.Results DRD1 gene and DRD3 gene showed significant effect on the body weight in mice in age of 21 day and 35 day, but at the age of 90 day, the differences became insignificant among the mice of various genetypes.Conclusions Dopamine may effect on the foraging and satiety in newborn mice through regulating the hypothalamic-pituitary-adrenal ( HPA ) axis activity, and finally leads to a reduced body weight gain in newborn mice and puppies during lactation.Furthermore, DRD1 gene and DRD3 gene may influence on body weight of newborn mice through regulating mothers’ lactation, lead to a lower body weight at ablactation, and compensatory increase of body weight after ablactation.Our results provide a substantial foundation for studying the function and interaction of DRD1 and DRD3 genes.