Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice
Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice
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DOI：
10.1016/j.neures.2010.06.004
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发表时间：
2010-10-01
影响因子：
2.9
通讯作者：
Ikeda, Joh-E
中科院分区：
文献类型：
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作者：
Hadano, Shinji;Yoshii, Yasuhiro;Ikeda, Joh-E
人类ALS 2的功能缺失突变导致了几种青少年隐性运动神经元疾病（MND）。为了了解ALS 2连锁MND中运动功能障碍的分子基础，迄今为止产生了具有混合遗传背景的几个Als 2（-/-）小鼠系，并彻底表征了它们的表型。然而，不同的Als 2-缺陷系之间的一些表型差异变得明显。为了研究遗传背景是否与这种差异相关，我们在这里产生了两种不同遗传背景的Als 2（-/-）小鼠的同源系; C57 BL/6（B6）和FVB/N（FVB），并研究了它们的总体表型。B6和FVB同源系均能育，无明显异常。在每种遗传背景下，野生型和Als 2（-/-）小鼠之间的生长曲线没有差异。非常好接受FVB而非B6背景的Als 2（-/-）小鼠表现出比野生型窝仔更短的寿命。此外，B6雌性而非雄性Als 2（-/-）小鼠显示出比野生型窝仔显著更低的自发性饲养活动。这些遗传背景和/或性别特异性研究结果表明，在Als 2（-/-）小鼠中存在寿命和运动活动的修饰剂。这些同源小鼠应提供一个有用的手段，了解MND的病理表型的可变表达的分子和遗传基础。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Loss-of-function mutations in human ALS2 account for several juvenile recessive motor neuron diseases (MNDs). To understand the molecular basis underlying motor dysfunction in ALS2-linked MNDs, several lines of Als2(-/-) mice with a mixed genetic background were thus far generated, and their phenotypes were thoroughly characterized. However, several phenotypic discrepancies among different Als2-deficient lines became evident. To investigate whether genetic backgrounds are associated with such discrepancies, we here generated congenic lines of Als2(-/-) mice on two different genetic backgrounds; C57BL/6 (B6) and FVB/N (FVB), and investigated their gross phenotypes. Both B6 and FVB congenic lines were viable and fertile with no evidences for obvious abnormalities. There were no differences in growth curves between wild-type and Als2(-/-) mice on each genetic background. Remarkably. Als2(-/-) mice on a FVB, but not a B6, background exhibited a shorter life span than wild-type litters. Further, B6 female, but not male, Als2(-/-) mice showed a significantly lower spontaneous rearing activity than wild-type litters. These genetic background- and/or gender-specific findings suggest the presence of modifiers for life span and motor activities in Als2(-/-) mice. These congenic mice should provide a useful means to understand the molecular and genetic basis for variable expression of pathological phenotypes in MNDs. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.