Wang Lishi, Jiao Yan, Sun Shuqiu, Jarrett Harry W, Sun Dianjun, Gu Weikuan
Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Department of Basic Medical Research, Inner Mongolia Medical University, Inner Mongolia, 010110, PR China.
Cell Biol Int. 2015 Jun;39(6):666-77. doi: 10.1002/cbin.10437. Epub 2015 Mar 2.
We previously identified the insertion of an intracisternal A-particle retrotransposons (IAPs) sequence in a gene, 9630033F20Rik, that contains domains involved in glycolysis from a mouse model called lethal wasting (lew). However, because both IAP insertion and the muation of vesicle-associated membrane protein 1 (VAMP1) were discovered from lew, the impact of the IAP insertion and Vamp1 on the lew mouse phenotype needs further investigation. In this study, the effect of the 9630033F20Rik and Vamp1 on glycolysis and muscle-wasting genes in heart, muscle, and brain tissues was further investigated using data of gene expression profiles in these tissues. Our data indicated that the expression levels of 9630033F20Rik and Vamp1 are not associated with each other. While 9630033F20Rik affects the expression of several key genes in pathways of glycolysis and muscle wasting, Vamp1 affects a different set of genes, with fewer numbers. In situ hybridization indicated that the expression of 9630033F20Rik is different in musculoskeletal tissues between the muscle-wasting mouse model and the wild-type model. Our data indicated that 9630033F20Rik may play an important role in muscle wasting and that it has a distinguished characterization of gene network. Our data also suggest that both 9630033F20Rik and Vamp1 play functional roles in muscle development and lead to the muscle-wasting phenotype when they are mutated.
我们之前在一个名为致死性消瘦(lew)的小鼠模型中,鉴定出一个基因(9630033F20Rik)插入了一个脑池内A颗粒逆转座子(IAPs)序列,该基因包含参与糖酵解的结构域。然而,由于在lew小鼠中同时发现了IAP插入和囊泡相关膜蛋白1(VAMP1)的突变,IAP插入和Vamp1对lew小鼠表型的影响需要进一步研究。在本研究中,利用这些组织中的基因表达谱数据,进一步研究了9630033F20Rik和Vamp1对心脏、肌肉和脑组织中糖酵解及肌肉消瘦相关基因的影响。我们的数据表明,9630033F20Rik和Vamp1的表达水平彼此不相关。虽然9630033F20Rik影响糖酵解和肌肉消瘦途径中几个关键基因的表达,但Vamp1影响的基因数量较少且不同。原位杂交表明,在肌肉消瘦小鼠模型和野生型模型的肌肉骨骼组织中,9630033F20Rik的表达存在差异。我们的数据表明,9630033F20Rik可能在肌肉消瘦中起重要作用,并且具有独特的基因网络特征。我们的数据还表明,9630033F20Rik和Vamp1在肌肉发育中都发挥功能作用,当它们发生突变时会导致肌肉消瘦表型。