Exploring novel genetic factors involved in sleep/wake regulation using inter-subspecific consomic strains established from MSM/Ms and C57BL/6J mice

使用从 MSM/Ms 和 C57BL/6J 小鼠建立的亚种间康体菌株探索参与睡眠/觉醒调节的新遗传因素

基本信息

批准号：
22500380
负责人：
TERAO Akira
金额：
$ 2.75万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Comprehensive phenotypic analysis was performed in B6-Chr5CMSM (5C)and B6-Chr5TMSM (5T), a consomic strain with 1-45cM and 41-86cM segments of chromosome5 from MSM on a B6 background, respectively. Their parental strains, C57BL/6J (B6), a commonly used laboratory mouse strain, and MSM, a wild-derived inbred mouse strain whose genetic background is diverse from that of B6, were analyzed in parallel. MSM chromosome5 in the context of a B6 genetic background conferred distinct differences in phenotypesfrom B6 controls. 5C had more consolidated sleep than B6. 5T had three distinct differences from B6 that can be summarized as follows: 1) The longest wake duration of 5T was 2.6times longer than that of B6; 2) Theta peak frequency (TPF) during rapid eye movementsleep in 5T was significantly lower than that in B6; 3) 5T showed occasional (up to 19 events in 30 min) spontaneous electroencephalogram (EEG) discharges lasting around 1second, which was not observed in B6. The amplitude of such EEG discharges was twice ashigh as that of the normal waking EEG level with a peak frequency of 6-8Hz. In order to examine the hereditary patterns of these three phenotypes identified between B6 and 5T,sleep/wake in (B6×5T)F1 was analyzed and the results were compared with that of B6 and5T. As a result, (B6×5T)F1 had B6-like phenotypes in terms of TPF and EEG dischargefrequency. Therefore, in the next step, linkage analysis was performed using{(B6×5T)F1×5T}N2. As a result, the genetic region associated with both the longest wake duration and EEG discharges was suggested to be located around D5Mit338 (59cM), and that associated with TPF to be located around D5Mit338 (59cM) and/or D5Mit141 (74cM).

在 B6-Chr5CMSM (5C) 和 B6-Chr5TMSM (5T) 中进行了全面的表型分析，B6-Chr5TMSM (5T) 是 B6 背景上 MSM 的 5 号染色体片段分别为 1-45cM 和 41-86cM 的康体菌株，它们的亲本菌株 C57BL/6J。 (B6) 是一种常用的实验室小鼠品系，MSM 是一种野生近交系小鼠品系，其遗传背景不同于在 B6 遗传背景下，对 B6 的染色体 5 进行了平行分析，结果显示，5C 与 B6 相比具有更巩固的睡眠，其与 B6 具有三个明显的差异： 1）5T的最长唤醒持续时间比B6长2.6倍；2）5T快速眼动睡眠时的Theta峰值频率（TPF）明显低于B6。 B6；3) 5T 偶尔出现持续约 1 秒的自发脑电图 (EEG) 放电，这种脑电图放电的幅度是正常清醒时脑电图水平的两倍。为了检查 B6 和 5T 之间确定的这三种表型的遗传模式，睡眠/唤醒的峰值频率为 6-8Hz。对(B6×5T)F1进行分析，并将结果与B6和5T进行比较，结果，(B6×5T)F1在TPF和EEG放电频率方面具有类似B6的表型，因此，在下一步中进行联动。使用{(B6×5T)F1×5T}N2进行分析，结果表明与最长觉醒持续时间和脑电图放电相关的遗传区域位于D5Mit338周围。 (59cM)，并且与 TPF 相关的位于 D5Mit338 (59cM) 和/或 D5Mit141 (74cM) 周围。