Functional replacement of myostatin with GDF-11 in the germline of mice.
Functional replacement of myostatin with GDF-11 in the germline of mice.
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DOI：
10.1186/s13395-022-00290-z
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发表时间：
2022-03-15
期刊：
影响因子：
4.9
通讯作者：
Germain-Lee EL
中科院分区：
文献类型：
--
作者：
Lee SJ;Lehar A;Rydzik R;Youngstrom DW;Bhasin S;Liu Y;Germain-Lee EL
肌肉生长抑素(MSTN)是一种转化生长因子超家族成员，是骨骼肌质量的主要调节因子。GDF-11与MSTN高度相关，在胚胎发育过程中发挥多种作用，包括调节中轴骨骼、肾脏、神经系统和胰腺的发育。由于MSTN和GDF-11具有高度的氨基酸序列同源性，在细胞培养分析中的表现几乎相同，并且使用相似的调节和信号成分，因此一个关键的问题是，它们不同的生物学功能是由于它们与特定调节和信号成分相互作用的能力的内在差异，还是它们不同的生物学功能主要反映了它们不同的时空表达模式。我们培育并鉴定了小鼠，在这些小鼠中，我们在种系中精确地将编码成熟C端肽的MSTN基因部分替换为Gdf11的相应区域。在敲入等位基因纯合的小鼠中，所有循环中的MSTN蛋白都被GDF-11取代，导致循环中GDF-11水平增加约30-40倍。携带敲入等位基因纯合的雄性小鼠肌肉重量略有下降，对高脂肪饮食的反应体重增加略有增加，血浆胆固醇和高密度脂蛋白水平略有上升，骨密度和骨量显著下降，而雌性小鼠几乎没有受到影响。GDF-11似乎能够在控制肌肉质量方面几乎完全取代MSTN。用GDF-11取代MSTN的发育和生理后果是非常有限的。
Myostatin (MSTN) is a transforming growth factor-ß superfamily member that acts as a major regulator of skeletal muscle mass. GDF-11, which is highly related to MSTN, plays multiple roles during embryonic development, including regulating development of the axial skeleton, kidneys, nervous system, and pancreas. As MSTN and GDF-11 share a high degree of amino acid sequence identity, behave virtually identically in cell culture assays, and utilize similar regulatory and signaling components, a critical question is whether their distinct biological functions result from inherent differences in their abilities to interact with specific regulatory and signaling components or whether their distinct biological functions mainly reflect their differing temporal and spatial patterns of expression. We generated and characterized mice in which we precisely replaced in the germline the portion of the Mstn gene encoding the mature C-terminal peptide with the corresponding region of Gdf11. In mice homozygous for the knock-in allele, all of the circulating MSTN protein was replaced with GDF-11, resulting in ~ 30–40-fold increased levels of circulating GDF-11. Male mice homozygous for the knock-in allele had slightly decreased muscle weights, slightly increased weight gain in response to a high-fat diet, slightly increased plasma cholesterol and HDL levels, and significantly decreased bone density and bone mass, whereas female mice were mostly unaffected. GDF-11 appears to be capable of nearly completely functionally replacing MSTN in the control of muscle mass. The developmental and physiological consequences of replacing MSTN with GDF-11 are strikingly limited.
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影响因子：
29
作者：
Egerman MA;Cadena SM;Gilbert JA;Meyer A;Nelson HN;Swalley SE;Mallozzi C;Jacobi C;Jennings LL;Clay I;Laurent G;Ma S;Brachat S;Lach-Trifilieff E;Shavlakadze T;Trendelenburg AU;Brack AS;Glass DJ
通讯作者：
Glass DJ
影响因子：
4.1
作者：
Guo W;Pencina KM;O'Connell K;Montano M;Peng L;Westmoreland S;Glowacki J;Bhasin S
通讯作者：
Bhasin S
Mstn基因敲除大鼠的建立及表型分析
DOI：
10.1016/j.bbrc.2016.06.030
发表时间：
2016-08-12
影响因子：
3.1
作者：
Gu, Hao;Cao, Yong;Yong, Weidong
通讯作者：
Yong, Weidong
DOI：
10.1073/pnas.1906253116
发表时间：
2019-07-30
影响因子：
11.1
作者：
Goebel, Erich J.;Corpina, Richard A.;Thompson, Thomas B.
通讯作者：
Thompson, Thomas B.
影响因子：
4.8
作者：
Hill, JJ;Davies, MV;Qiu, YC
通讯作者：
Qiu, YC