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对小鹿斑比毛色(FH/Wjd)大鼠这一抑郁症与酒精中毒共病动物模型的进一步基因特征分析。

Further genetic characterization of the fawn-hooded (FH/Wjd) rat, an animal model of comorbid depression and alcoholism.

作者信息

Rezvani Amir H, Overstreet David H, Cleves Mario, Parsian Abbas

机构信息

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

Psychiatr Genet. 2007 Apr;17(2):77-83. doi: 10.1097/YPG.0b013e328012d7c3.

Abstract

OBJECTIVE

The main objective of this study was a more detailed genetic characterization of the alcohol preferring fawn-hooded rat and its intercrosses. Fawn-hooded rats drink substantially more alcohol voluntarily than the ACI rats. The fawn-hooded rats were shown to be more immobile in the forced-swimming test and to drink more saccharin. Recent comparisons of the parental strains with F1 and F2 intercrosses revealed that the alcohol and saccharin intakes were positively correlated with each other but not with immobility.

METHODS

The F1 and F2 progeny were generated by intercrossing the fawn-hooded and ACI/N rats. Data from the F2 progeny, their F1 parents and progenitors were used to estimate heritability.

RESULTS

Heritability was estimated for alcohol intake (75.6% in males and 67.1% in females), alcohol preference (64.7% in males and 39.2% in females), saccharin intake (50.8% in males and 37.5% in females), and immobility (50.2% in males and 72.1% in females). This same data provided estimates of the number of genes involved in these phenotypes between three and six. We also took advantage of the fact that both progenitor strains are pigmented, so a tremendous variety of coat colors were present in the F2 progeny (i.e. black, black-hooded, agouti, agouti-hooded, fawn, fawn-hooded, orange, and orange-hooded). Coat color analyses indicated that none of the variables significantly varied with coat color. A high correlation however, was observed between alcohol intake and preference in each group. Significant correlations between alcohol and saccharin intakes were seen only in some groups.

CONCLUSION

These findings suggest that these phenotypes might be regulated by multiple genes, which could be detected in quantitative trait loci. These analyses are currently underway and will provide a novel approach in understanding the genetics of voluntary alcohol drinking.

摘要

目的

本研究的主要目的是对嗜酒型淡褐 hooded 大鼠及其杂交后代进行更详细的基因特征分析。淡褐 hooded 大鼠自愿饮用的酒精量显著多于 ACI 大鼠。在强迫游泳试验中,淡褐 hooded 大鼠表现出更多的不动行为,且饮用更多的糖精。最近对亲本品系与 F1 和 F2 杂交后代的比较显示,酒精和糖精摄入量彼此呈正相关,但与不动行为无关。

方法

通过将淡褐 hooded 大鼠与 ACI/N 大鼠杂交产生 F1 和 F2 后代。来自 F2 后代、其 F1 亲本及祖代的数据用于估计遗传力。

结果

估计了酒精摄入量(雄性为 75.6%,雌性为 67.1%)、酒精偏好(雄性为 64.7%,雌性为 39.2%)、糖精摄入量(雄性为 50.8%,雌性为 37.5%)和不动行为(雄性为 50.2%,雌性为 72.1%)的遗传力。相同的数据提供了参与这些表型的基因数量在 3 到 6 个之间的估计值。我们还利用了两个祖代品系均有色素沉着这一事实,因此 F2 后代中出现了各种各样的毛色(即黑色、黑 hooded、刺鼠色、刺鼠色 hooded、淡褐色、淡褐 hooded、橙色和橙色 hooded)。毛色分析表明,没有一个变量随毛色有显著变化。然而,在每个组中都观察到酒精摄入量与偏好之间存在高度相关性。仅在某些组中观察到酒精和糖精摄入量之间存在显著相关性。

结论

这些发现表明,这些表型可能受多个基因调控,这些基因可在数量性状基因座中检测到。目前正在进行这些分析,这将为理解自愿饮酒的遗传学提供一种新方法。

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