Complex trait analysis of the hippocampus: Mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice
Complex trait analysis of the hippocampus: Mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice
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DOI：
10.1523/jneurosci.21-10-03503.2001
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发表时间：
2001-05-15
影响因子：
5.3
通讯作者：
Williams, RW
中科院分区：
文献类型：
--
作者：
Lu, L;Airey, DC;Williams, RW
海马结构的显著差异与发育和行为能力的有趣差异有关。我们探讨了遗传和环境因素，调节海马的大小，结构和细胞数量使用C57 BL/6 J（B6）和DBA/2 J（D2）小鼠集;他们的F1和F2杂交（n = 180）;和35行BXD重组近交系（RI）菌株。亲本菌株的海马重量相差20%。颗粒细胞数量的估计值也相差约20%。RI品系的海马重量范围为21至31 mg，个体F2小鼠的海马重量范围为23至36 mg（双侧重量）。体积与颗粒细胞数呈良好的相关性（r = 0.7 ~ 0.8）。年龄和性别的差异与显著差异有关。海马体的重量每月增加0.24毫克，男性海马体的重量增加0.55毫克变异的遗传力接近50%，并且这种遗传变异的一半是由两个定位于1号染色体的数量性状基因座产生的（Hippla：全基因组p < 0.005，在65和100 cM之间）和5号染色体（Hipp 5a，p < 0.05，在15和40 cM之间）。这些是已知的第一个在前脑结构中产生正常变异的基因位点。Hipp 1a和Hipp 5a分别调节海马重量1.0- 2.0毫克，效果大小大于年龄或性别产生的。Hipp基因座调节齿状回中的神经元数量，共同将群体上下移动多达20万个细胞。Hipp基因座的候选基因包括Rxrg和Fgfr 3。
Notable differences in hippocampal structure are associated with intriguing differences in development and behavioral capabilities. We explored genetic and environmental factors that modulate hippocampal size, structure, and cell number using sets of C57BL/6J (B6) and DBA/2J (D2) mice; their F1 and F2 intercrosses (n = 180); and 35 lines of BXD recombinant inbred (RI) strains. Hippocampal weights of the parental strains differ by 20%. Estimates of granule cell number also differ by similar to 20%. Hippocampal weights of RI strains range from 21 to 31 mg, and those of individual F2 mice range from 23 to 36 mg (bilateral weights). Volume and granule cell number are well correlated (r = 0.7- 0.8). Significant variation is associated with differences in age and sex. The hippocampus increases in weight by 0.24 mg per month, and those of males are 0.55 mg heavier (bilateral) than those of females.Heritability of variation is similar to 50%, and half of this genetic variation is generated by two quantitative trait loci that map to chromosome 1 (Hipp1a: genome- wide p < 0.005, between 65 and 100 cM) and to chromosome 5 (Hipp5a, p < 0.05, between 15 and 40 cM). These are among the first gene loci known to produce normal variation in forebrain structure. Hipp1a and Hipp5a individually modulate hippocampal weight by 1.0- 2.0 mg, an effect size greater than that generated by age or sex. The Hipp gene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for the Hipp loci include Rxrg and Fgfr3.