Pannexin 1 Transgenic Mice: Human Diseases and Sleep-Wake Function Revision.
Pannexin 1 Transgenic Mice: Human Diseases and Sleep-Wake Function Revision.
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DOI：
10.3390/ijms22105269
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发表时间：
2021-05-17
影响因子：
5.6
通讯作者：
Panchin Y
中科院分区：
文献类型：
--
作者：
Battulin N;Kovalzon VM;Korablev A;Serova I;Kiryukhina OO;Pechkova MG;Bogotskoy KA;Tarasova OS;Panchin Y
在人类和其他脊椎动物中，Pannexin蛋白家族是通过与无脊椎动物的缝隙连接蛋白同源而发现的。许多生物学功能都归因于三种脊椎动物的膜联结蛋白成员。6个具有临床意义的Panx1基因独立变异导致人类不孕不育和卵母细胞发育缺陷，Arg217His变异与明显的症状相关，如原发性卵巢衰竭、严重智能障碍、感音神经性听力损失和脊柱后凸。与此同时，在Panx1基因敲除小鼠中仅观察到轻微的表型。此外，在一种广受欢迎的Panx1基因敲除小鼠品系中发现了乘客突变，这甚至质疑了这些影响。利用CRISPR/Cas9，我们创造了一个新的Panx1基因敲除小鼠品系和一个具有临床意义的Panx1替代小鼠品系(Arg217His)。在这两种情况下，我们都没有观察到老鼠大小、体重或生育能力的显著变化。此外，我们试图重现之前对Panx1基因敲除小鼠的睡眠/觉醒和运动活动功能的研究，发现之前报道的影响可能不是由Panx1基因敲除本身引起的。我们认为，Arg217H在Panx1中的病理作用是替换，一些Panx1的一般功能需要重新评估。
In humans and other vertebrates pannexin protein family was discovered by homology to invertebrate gap junction proteins. Several biological functions were attributed to three vertebrate pannexins members. Six clinically significant independent variants of the PANX1 gene lead to human infertility and oocyte development defects, and the Arg217His variant was associated with pronounced symptoms of primary ovarian failure, severe intellectual disability, sensorineural hearing loss, and kyphosis. At the same time, only mild phenotypes were observed in Panx1 knockout mice. In addition, a passenger mutation was identified in a popular line of Panx1 knockout mice, questioning even those effects. Using CRISPR/Cas9, we created a new line of Panx1 knockout mice and a new line of mice with the clinically significant Panx1 substitution (Arg217His). In both cases, we observed no significant changes in mouse size, weight, or fertility. In addition, we attempted to reproduce a previous study on sleep/wake and locomotor activity functions in Panx1 knockout mice and found that previously reported effects were probably not caused by the Panx1 knockout itself. We consider that the pathological role of Arg217His substitution in Panx1, and some Panx1 functions in general calls for a re-evaluation.
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影响因子：
3.5
作者：
Marziano, NK;Casalotti, SO;Forge, A
通讯作者：
Forge, A
DOI：
10.1073/pnas.2233464100
发表时间：
2003-11-11
影响因子：
11.1
作者：
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影响因子：
5.5
作者：
Gaynullina D;Tarasova OS;Kiryukhina OO;Shestopalov VI;Panchin Y
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Panchin Y
影响因子：
2.9
作者：
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通讯作者：
Tobler, I
DOI：
10.1073/pnas.1018262108
发表时间：
2011-12-20
影响因子：
11.1
作者：
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通讯作者：
Schwaninger, Markus