Coschigano K T, Wetzel A N, Obichere N, Sharma A, Lee S, Rasch R, Guigneaux M M, Flyvbjerg A, Wood T G, Kopchick J J
Department of Biomedical Sciences, College of Osteopathic Medicine, 228 Irvine Hall, Ohio University, Athens, OH 45701, USA.
Growth Horm IGF Res. 2010 Oct;20(5):345-55. doi: 10.1016/j.ghir.2010.06.001. Epub 2010 Jul 23.
Bovine growth hormone (bGH) transgenic mice develop severe kidney damage. This damage may be due, at least in part, to changes in gene expression. Identification of genes with altered expression in the bGH kidney may identify mechanisms leading to damage in this system that may also be relevant to other models of kidney damage.
cDNA subtraction libraries, northern blot analyses, microarray analyses and real-time reverse transcription polymerase chain reaction (RT/PCR) assays were used to identify and verify specific genes exhibiting differential RNA expression between kidneys of bGH mice and their non-transgenic (NT) littermates.
Immunoglobulins were the vast majority of genes identified by the cDNA subtractions and the microarray analyses as being up-regulated in bGH. Several glycoprotein genes and inflammation-related genes also showed increased RNA expression in the bGH kidney. In contrast, only a few genes were identified as being significantly down-regulated in the bGH kidney. The most notable decrease in RNA expression was for the gene encoding kidney androgen-regulated protein.
A number of genes were identified as being differentially expressed in the bGH kidney. Inclusion of two groups, immunoglobulins and inflammation-related genes, suggests a role of the immune system in bGH kidney damage.
牛生长激素(bGH)转基因小鼠会出现严重的肾脏损伤。这种损伤可能至少部分归因于基因表达的变化。鉴定bGH转基因小鼠肾脏中表达改变的基因,可能会找出导致该系统损伤的机制,而这些机制可能也与其他肾脏损伤模型相关。
利用cDNA消减文库、Northern印迹分析、微阵列分析和实时逆转录聚合酶链反应(RT/PCR)检测,来鉴定和验证在bGH转基因小鼠及其非转基因(NT)同窝小鼠的肾脏之间表现出RNA表达差异的特定基因。
免疫球蛋白是通过cDNA消减和微阵列分析鉴定出的在bGH转基因小鼠中上调的绝大多数基因。几个糖蛋白基因和炎症相关基因在bGH转基因小鼠的肾脏中也显示出RNA表达增加。相比之下,只有少数基因被鉴定为在bGH转基因小鼠的肾脏中显著下调。RNA表达下降最明显的是编码肾脏雄激素调节蛋白的基因。
已鉴定出一些在bGH转基因小鼠肾脏中差异表达的基因。其中包括免疫球蛋白和炎症相关基因这两类,提示免疫系统在bGH转基因小鼠肾脏损伤中发挥作用。