Jiao Yan, Jin Xiudong, Yan Jian, Jiao Feng, Li Xinmin, Roe Bruce A, Jarrett Harry W, Gu Weikuan
Departments of Orthopaedic Surgery- Campbell Clinic and Pathology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Genes Genet Syst. 2009 Oct;84(5):327-34. doi: 10.1266/ggs.84.327.
Intracisternal A-particle retrotransposons (IAPs) are known, moveable, retrovirus-like elements and are defective in envelope protein synthesis in the mouse genome. Insertion of IAP elements can either interupt or enhance gene function or expression. Using a mouse model called lethal wasting (lew), we recently identified the insertion of an IAP sequence in a gene, 9630033F20Rik, that contains domains involved in glycolysis. The expression pattern of the 9630033F20Rik gene between various normal and diseased tissues was determined by semi-quantitative RT-PCR. The effect of the insertion mutation in 9630033F20Rik on glycolysis in heart, muscle, and brain tissues was further investigated using oligonuleotide microarray analysis. Results indicated that the expression of 9630033F20Rik is ubiquitous and its signal is relatively higher in heart and brain tissues. The insertion caused the deletion of exon 5 and decreased expression of this gene in all the tissues studied in the lew mice. Changes in the expression levels of glycolytic genes mainly occured in muscle tissue, raising a possibility that 9630033F20Rik may function as one of the transcriptional regulators of glycolytic genes in skeletal muscle. However, considering the fact that a single nucleotide mutation in vesicle-associated membrane protein 1 (VAMP1) has been reported as the causal gene for the lew mouse, how much of an impact the IAP insertion in the lew mouse phenotype has on glycolytic genes compared to the effect from the VAMP1 mutation responsible for the lew mouse phenotype should be further investigated.
脑池内A颗粒逆转录转座子（IAPs）是已知的、可移动的、类似逆转录病毒的元件，在小鼠基因组中包膜蛋白合成存在缺陷。IAP元件的插入可中断或增强基因功能或表达。利用一种名为致死性消瘦（lew）的小鼠模型，我们最近在一个名为9630033F20Rik的基因中发现了一个IAP序列的插入，该基因包含参与糖酵解的结构域。通过半定量RT-PCR确定了9630033F20Rik基因在各种正常和患病组织之间的表达模式。使用寡核苷酸微阵列分析进一步研究了9630033F20Rik中插入突变对心脏、肌肉和脑组织糖酵解的影响。结果表明，9630033F20Rik的表达普遍存在，其信号在心脏和脑组织中相对较高。该插入导致第5外显子缺失，并降低了lew小鼠所有研究组织中该基因的表达。糖酵解基因表达水平的变化主要发生在肌肉组织中，这增加了9630033F20Rik可能作为骨骼肌中糖酵解基因转录调节因子之一发挥作用的可能性。然而，考虑到囊泡相关膜蛋白1（VAMP1）中的单核苷酸突变已被报道为lew小鼠的致病基因，与导致lew小鼠表型的VAMP1突变相比，lew小鼠表型中的IAP插入对糖酵解基因的影响程度仍有待进一步研究。
