MULTIPLE DEFECTS AND PERINATAL DEATH IN MICE DEFICIENT IN FOLLISTATIN
MULTIPLE DEFECTS AND PERINATAL DEATH IN MICE DEFICIENT IN FOLLISTATIN
复制标题
DOI：
10.1038/374360a0
复制
发表时间：
1995-03-23
期刊：
影响因子：
64.8
通讯作者：
BRADLEY, A
中科院分区：
文献类型：
--
作者：
MATZUK, MM;LU, NF;BRADLEY, A
FOLLISTATIN是一种体外激活素结合蛋白和激活素拮抗剂（1，2），可与硫酸乙酰肝素蛋白聚糖结合（3），并可在体内将激活素呈递给其受体。在小鼠中，卵泡抑素信使RNA首先在蜕膜中检测到（在胚胎第5.5天），随后在发育中的后脑、体节、触须、牙齿、表皮和肌肉中检测到（4-11）。在非洲爪蟾中，卵泡抑素的过度表达导致神经组织的诱导（12）。在这里，我们使用功能缺失突变小鼠来研究卵泡抑素在哺乳动物中的功能。我们发现，卵泡抑素缺乏的小鼠生长迟缓，横膈膜和肋间肌质量下降，皮肤光泽紧绷，硬腭和第十三对肋骨的骨骼缺陷，胡须和牙齿发育异常，它们无法呼吸，并在出生后几小时内死亡。这些缺陷比在激活素缺陷突变螨中所见的缺陷更普遍，表明卵泡抑素可能调节转化生长因子β家族的几个成员的作用。
FOLLISTATIN, an activin-binding protein and activin antagonist in vitro(1,2), can bind to heparan sulphate proteoglycans(3) and may function in vivo to present activins to their receptors. In the mouse, follistatin messenger RNA is first detected in the deciduum (on embryonic day 5.5), and later in the developing hindbrain, somites, vibrissae, teeth, epidermis and muscle(4-11). In Xenopus laevis, overexpression of follistatin leads to induction of neural tissue(12). Here we use loss-of-function mutant mice to investigate the function of follistatin in mammals. We find that follistatin-deficient mice are retarded in their growth, have decreased mass of the diaphragm and intercostal muscles, shiny taut skin, skeletal defects of the hard palate and the thirteenth pair of ribs, their whisker and tooth development is abnormal, they fail to breathe, and die within hours of birth. These defects are more widespread than those seen in activin-deficient mutant mite, indicating that follistatin may modulate the actions of several members of the transforming growth factor-beta family.