Reiss K, Cheng W, Ferber A, Kajstura J, Li P, Li B, Olivetti G, Homcy C J, Baserga R, Anversa P
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8630-5. doi: 10.1073/pnas.93.16.8630.
Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from transgenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight was comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, and 300 days, respectively, after birth. At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and control mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.
构建了转基因小鼠，其中人胰岛素样生长因子1B（IGF-1B）的cDNA置于大鼠α-肌球蛋白重链启动子的控制之下。在转基因杂合子小鼠中，妊娠末期胎儿心脏中检测不到IGF-1B mRNA，出生后1天含量适中，并随着出生后成熟而逐渐增加，在75天时达到峰值。从转基因小鼠分离的心肌细胞每10(6)个细胞每24小时分泌1.15±0.25 ng的IGF-1，而来自纯合野生型同窝小鼠的心肌细胞分泌量为0.27±0.10 ng。转基因小鼠的血浆IGF-1水平增加了84%。在45日龄之前，野生型同窝小鼠和转基因小鼠的心脏重量相当，但出生后75、135、210和300天时分别增加了42%、45%、62%和51%。在45、75和210天时，转基因动物心脏中的心肌细胞数量分别高出21%、31%和55%。相比之下，转基因小鼠和对照小鼠在所有年龄段的心肌细胞体积相当。总之，心肌细胞中IGF-1的过表达导致心脏肥大，这是由心脏中细胞数量增加介导的。
