Heterozygous deletion of sarcolipin maintains normal cardiac function.
Heterozygous deletion of sarcolipin maintains normal cardiac function.
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肌磷脂的杂合缺失维持正常的心脏功能。
DOI：
10.1152/ajpheart.00411.2015
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Minamisawa S.
中科院分区：
文献类型：
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作者：
Shimura D;Kusakari Y;Sasano T;Nakashima Y;Nakai G;Jiao Q;Jin M;Yokota T;Ishikawa Y;Nakano A;Goda N;Minamisawa S.
肌磷脂（Sarcolipin，SLN）是一种小分子蛋白脂质，是肌浆网Ca~（2+）-ATP酶的调节剂。在心脏组织中，SLN仅在心房中表达。先前，我们通过同源重组将Cre重组酶插入到内源性SLN基因座中，并成功地产生SLN-Cre敲入（SlnCre/+）小鼠。该SlnCre/+小鼠可用于产生心房特异性基因靶向突变体，并且其基于Cre-loxP系统。在本研究中，我们使用成年SlnCre/+小鼠心房，并在用作基因打靶小鼠之前分析通过Cre敲入杂合SLN缺失的影响。SLN mRNA和蛋白水平在SlnCre/+小鼠心房中均降低，但没有形态学、生理学或分子生物学异常。收缩性和Ca2+处理的特性与野生型（WT）小鼠相似，并且SlnCre/+和WT小鼠之间的几种应激标志物的表达水平和肌浆网相关蛋白水平没有差异。肌浆网Ca~（2+）-ATP酶活性两组间无显著性差异。我们表明，SlnCre/+小鼠在检查的所有方面与WT小鼠没有显著差异。本研究提供了SlnCre/+小鼠的基本特征，并可能提供关于SlnCre/+小鼠作为心房特异性基因靶向模型的有用性的信息。
Sarcolipin (SLN) is a small proteolipid and a regulator of sarco(endo)plasmic reticulum Ca2+-ATPase. In heart tissue, SLN is exclusively expressed in the atrium. Previously, we inserted Cre recombinase into the endogenous SLN locus by homologous recombination and succeeded in generating SLN-Cre knockin (SlnCre/+) mice. This SlnCre/+mouse can be used to generate an atrium-specific gene-targeting mutant, and it is based on the Cre-loxP system. In the present study, we used adult SlnCre/+mice atria and analyzed the effects of heterozygous SLN deletion by Cre knockin before use as the gene targeting mouse. Both SLN mRNA and protein levels were decreased in SlnCre/+mouse atria, but there were no morphological, physiological, or molecular biological abnormalities. The properties of contractility and Ca2+handling were similar to wild-type (WT) mice, and expression levels of several stress markers and sarcoplasmic reticulum-related protein levels were not different between SlnCre/+and WT mice. Moreover, there was no significant difference in sarco(endo)plasmic reticulum Ca2+-ATPase activity between the two groups. We showed that SlnCre/+mice were not significantly different from WT mice in all aspects that were examined. The present study provides basic characteristics of SlnCre/+mice and possibly information on the usefulness of SlnCre/+mice as an atrium-specific gene-targeting model.