白化病对乙醇和麻醉剂的镇静催眠敏感性无影响。

No effect of albinism on sedative-hypnotic sensitivity to ethanol and anesthetics.

作者信息

Rikke B A, Simpson V J, Montoliu L, Johnson T E

机构信息

Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447, USA.

出版信息

Alcohol Clin Exp Res. 2001 Feb;25(2):171-6.

PMID:11236829

Abstract

BACKGROUND

Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS) intercrosses have found genetic linkage between Tyr albinism (c/c) and differential sensitivity to sedative-hypnotic doses of ethanol and general anesthetics. This linkage could be due to a gene or genes near Tyr or Tyr itself. With regard to the latter possibility, the absence of tyrosinase activity (encoded by Tyr) in albinos could alter tyrosine availability and thus the rate-limiting step in catecholamine synthesis. In addition, albinism is associated with altered brain development that could have pleiotropic effects on behavior. Therefore, in this study, we asked whether albinism affects sedative-hypnotic sensitivity.

METHODS

Loss of righting reflex (LORR) duration was measured using doses of ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and etomidate (20 mg/kg) that were previously associated with differential sensitivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were backcrossed to ISS (c/c) to compare pigmented (c/c, Tg(Tyr+)) and albino (c/c) mice in the context of an ISS-like background. ISS was also crossed with C57BL/6 (B6) mice heterozygous for a spontaneous albino mutation (c2j) to compare pigmented (c/+) and albino (c/c2j) mice. Pigmented B6 (c2j/+ and +/+) and albino B6 (c2j/c2j) mice were also compared (pentobarbital).

RESULTS

For each sedative hypnotic, albinism had no effect on LORR duration. Each expected difference was ruled out at the 95% or 99% confidence level. For each sedative hypnotic, males were more sensitive than females even though the effect size was usually smaller than the expected albino effect size, arguing empirically that the inability to detect an albino effect was not due to systematic error or an insufficient number of mice.

CONCLUSION

We conclude that the differential sensitivity associated with albinism is most likely due to a gene or genes near Tyr rather than Tyr itself.

摘要

背景

使用长睡眠（LS）×短睡眠（SS）（LSXSS）重组近交系小鼠以及近交长睡眠（ILS）与近交短睡眠（ISS）杂交的研究发现，酪氨酸白化病（c/c）与对镇静催眠剂量乙醇和全身麻醉剂的敏感性差异之间存在遗传连锁。这种连锁可能归因于酪氨酸附近的一个或多个基因，或者酪氨酸本身。关于后一种可能性，白化病小鼠中缺乏酪氨酸酶活性（由Tyr编码）可能会改变酪氨酸的可用性，从而影响儿茶酚胺合成中的限速步骤。此外，白化病与大脑发育改变有关，这可能对行为产生多效性影响。因此，在本研究中，我们探究了白化病是否会影响镇静催眠敏感性。

方法

使用先前与白化病和非白化病小鼠敏感性差异相关的乙醇剂量（4.1 g/kg）、戊巴比妥剂量（70 mg/kg）、异氟烷剂量（2 g/kg）和依托咪酯剂量（20 mg/kg）来测量翻正反射消失（LORR）持续时间。将酪氨酸转基因小鼠（c/c，Tg(Tyr+)）与ISS（c/c）回交，以比较在类似ISS背景下的有色小鼠（c/c，Tg(Tyr+)）和白化病小鼠（c/c）。ISS还与携带自发白化病突变（c2j）的C57BL/6（B6）杂合小鼠杂交，以比较有色小鼠（c/+）和白化病小鼠（c/c2j）。还比较了有色B6小鼠（c2j/+和+/+）和白化病B6小鼠（c/c2j）（戊巴比妥）。