Abstract—In order to investigate the joint influence of C1473G polymorphism in the gene encoding the key enzyme for serotonin (5-HT) biosynthesis in brain – tryptophan hydroxylase-2, and the distal fragment (103,9-112,4 Мbp) of chromosome 13, including 5-HT1A serotonin receptor gene from catalepsy-prone CBA strain, on the brain 5-HT system, new recombinant mice strain B6-1473GG.CBA-CD13Mit76С (1473GG-76C) and B6-1473GG.CBA-D13Mit76В (1473GG-76B) on the base of C57BL/6 strain were created. The 1473GG-76C and 1473GG-76B lines carry a fragment of chromosome 13 containing Htr1a gene from the CBA and the C57BL/6 strains respectively. Both lines are homozygous by 1473G-allele, reducing the activity of TPH-2. It was shown that the 1473GG-76C line is characterized by increased levels of mRNA of Htr1a, Htr2a genes and Maoa gene (monoamine oxidase type A—the main enzyme of 5-HT degradation) in the midbrain, Htr1a gene in the cortex, Htr1a and Htr2a genes in the hippocampus as compared to 1473GG-76B. In addition, the 1473GG-76C line has increased expression of genes encoding the key regulators of Htr1a gene—FREUD-1 and FREUD-2. The mRNA level of the Cc2d1a gene encoding FREUD-1 was increased in the cortex, and the expression of the Cc2d1b gene encoding FREUD-2 was enhanced in the midbrain. Also, the 1473GG-76C line has increased 5-HT levels in the midbrain, hypothalamus and hippocampus. At the same time, the level of the main 5-HT metabolite, 5-HIAA, was decreased in the midbrain and cortex of these mice. The ratio of 5-HIAA/5-HT reflecting the intensity of 5-HT metabolism was reduced in all investigated structures of 1473GG-76C mice. Thus, the combination of 1473G-allelele of Tph2 gene with Htr1a gene from the CBA strain had a significant effect on the mRNA levels of the key genes of the 5-HT system and on 5-HT metabolism in the brain of 1473GG-76C mice.

摘要—为了研究C1473G基因多态性对脑中5-羟色胺（5-HT）生物合成关键酶编码基因色氨酸羟化酶2和其远端片段（103,9-112,4Мbp）的共同影响第13号染色体，包括来自容易发作的CBA株的5-HT1A血清素受体基因，位于大脑5-HT系统上，新的重组小鼠株B6-1473GG.CBA-CD13Mit76С（1473GG-76C）和B6-1473GG.CBA-D13Mit76В（在C57BL / 6菌株的基础上产生了1473GG-76B）。1473GG-76C和1473GG-76B品系分别携带来自CBA和C57BL / 6菌株的Htr1a基因的13号染色体片段。两条线均由1473G等位基因纯合，从而降低了TPH-2的活性。结果表明1473GG-76C品系的特征在于其mRNA水平的升高HTR1A，HTR2A基因和MAOA中脑基因（单胺氧化酶A型主5-HT降解酶），HTR1A在皮质基因，HTR1A和HTR2A在海马基因相比1473GG-76B。此外，1473GG-76C品系增加了编码Htr1a基因的关键调控因子FREUD-1和FREUD-2的基因的表达。编码FREUD-1的Cc2d1a基因的mRNA水平在皮层中增加，并且Cc2d1b的表达编码FREUD-2的基因在中脑中得到增强。同样，1473GG-76C品系在中脑，下丘脑和海马中的5-HT水平升高。同时，这些小鼠的中脑和皮层中主要的5-HT代谢产物5-HIAA的水平降低了。在1473GG-76C小鼠的所有研究结构中，反映5-HT代谢强度的5-HIAA / 5-HT的比例均降低。因此，1473G-allelele的组合TPH2基因与HTR1A从CBA品系基因在1473GG-76C的小鼠的脑在5-HT系统的关键基因的mRNA水平的显著作用和对5-HT的代谢。