Mutations in Alström protein impair terminal differentiation of cardiomyocytes.
Mutations in Alström protein impair terminal differentiation of cardiomyocytes.
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DOI：
10.1038/ncomms4416
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发表时间：
2014-03-04
影响因子：
16.6
通讯作者：
Judge, Daniel P.
中科院分区：
文献类型：
--
作者：
Shenje, Lincoln T.;Andersen, Peter;Halushka, Marc K.;Lui, Cecillia;Fernandez, Laviel;Collin, Gayle B.;Amat-Alarcon, Nuria;Meschino, Wendy;Cutz, Ernest;Chang, Kenneth;Yonescu, Raluca;Batista, Denise A. S.;Chen, Yan;Chelko, Stephen;Crosson, Jane E.;Scheel, Janet;Vricella, Luca;Craig, Brian D.;Marosy, Beth A.;Mohr, David W.;Hetrick, Kurt N.;Romm, Jane M.;Scott, Alan F.;Valle, David;Naggert, Juergen K.;Kwon, Chulan;Doheny, Kimberly F.;Judge, Daniel P.
哺乳动物的心肌细胞分裂和复制在胚胎发育过程中进行，并在出生后不久突然衰退。心肌细胞细胞周期停滞的控制过程尚不清楚。在这里，我们对婴儿进行全外显子组测序，并有出生后心肌细胞持续复制的证据，以确定遗传风险因素。我们在先证者中鉴定出复合杂合 ALMS1 突变，并确认其在她受影响的兄弟姐妹中的存在，每个杂合父母都有一个拷贝。接下来，我们在其他四名出生后心肌细胞增殖水平较高的儿童中发现了 ALMS1 的纯合或复合杂合截短突变。 Alms1 mRNA 敲低增加了心肌细胞增殖的多种标志物、G2/M 期心肌细胞的百分比以及培养细胞中心肌细胞的数量增加 10%。与野生型同窝小鼠相比，纯合 Alms1 突变小鼠出生后两周心肌细胞增殖增加。我们得出的结论是，Alström 蛋白的缺乏会损害出生后心肌细胞细胞周期停滞。
Cardiomyocyte cell division and replication in mammals proceed through embryonic development and abruptly decline soon after birth. The process governing cardiomyocyte cell cycle arrest is poorly understood. Here we carry out whole exome sequencing in an infant with evidence of persistent postnatal cardiomyocyte replication to determine the genetic risk factors. We identify compound heterozygous ALMS1 mutations in the proband, and confirm their presence in her affected sibling, one copy inherited from each heterozygous parent. Next, we recognise homozygous or compound heterozygous truncating mutations in ALMS1 in four other children with high levels of postnatal cardiomyocyte proliferation. Alms1 mRNA knockdown increases multiple markers of proliferation in cardiomyocytes, the percentage of cardiomyocytes in G2/M phases, and the number of cardiomyocytes by 10% in cultured cells. Homozygous Alms1-mutant mice have increased cardiomyocyte proliferation at two weeks postnatal compared to wild-type littermates. We conclude that deficiency of Alström protein impairs postnatal cardiomyocyte cell cycle arrest.
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影响因子：
8
作者：
Fielding, Andrew B.;Royle, Stephen J.
通讯作者：
Royle, Stephen J.
DOI：
10.1073/pnas.0704044104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Kwon, Chulan;Arnold, Joshua;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
心脏成纤维细胞通过Beta1整合素信号传导调节心肌增殖。
影响因子：
11.8
作者：
Leda, Masaki;Tsuchihashi, Takatoshi;Ivey, Kathryn N.;Ross, Robert S.;Hong, Ting-Ting;Shaw, Robin M.;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
3.3
作者：
Knorz VJ;Spalluto C;Lessard M;Purvis TL;Adigun FF;Collin GB;Hanley NA;Wilson DI;Hearn T
通讯作者：
Hearn T
影响因子：
30.8
作者：
Collin, GB;Marshall, JD;Naggert, JK
通讯作者：
Naggert, JK