Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow.
Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow.
复制标题
作者：
Bhatwadekar AD;Yan Y;Qi X;Thinschmidt JS;Neu MB;Li Calzi S;Shaw LC;Dominiguez JM;Busik JV;Lee C;Boulton ME;Grant MB
在这项研究中，我们评估了Per 2时钟基因突变小鼠是否表现出类似于糖尿病的血管表型。使用4月龄和12月龄的Per 2（B6.129-Per 2 tm 1Drw/J）或野生型对照小鼠。为了评估Per 2突变小鼠中的糖尿病样表型，定量视网膜的mRNA表达，并评估糖尿病视网膜病变的程度。通过对股骨进行酪氨酸羟化酶（TH）和神经丝200（NF-200）染色来研究骨髓神经病。进行骨髓祖细胞（BMPC）的增殖和定量的速率，并且在Per 2突变小鼠中观察到增殖减少三倍和一氧化氮水平减少50%。TH阳性神经突起和NF-200染色在Per 2突变小鼠中减少。视网膜内皮型一氧化氮合酶的蛋白质和mRNA表达均降低了两倍。其他内皮功能基因（VEGFR 2、VEGFR 1）在Per 2突变体视网膜中下调（1.5-2倍），而转化生长因子-β1介导的促纤维化途径上调。我们的研究表明，Per 2突变小鼠重现了糖尿病的关键方面，而没有代谢异常，包括视网膜血管损伤，骨髓神经元丢失和BMPC功能减弱。
In this study, we assessed whether Per2 clock gene–mutant mice exhibit a vascular phenotype similar to diabetes. Per2 (B6.129-Per2tm1Drw/J) or wild-type control mice 4 and 12 months of age were used. To evaluate diabetes-like phenotype in Per2 mutant mice, retina was quantified for mRNA expression, and degree of diabetic retinopathy was evaluated. Bone marrow neuropathy was studied by staining femurs for tyrosine hydroxylase (TH) and neurofilament 200 (NF-200). The rate of proliferation and quantification of bone marrow progenitor cells (BMPCs) was performed, and a threefold decrease in proliferation and 50% reduction in nitric oxide levels were observed in Per2 mutant mice. TH-positive nerve processes and NF-200 staining were reduced in Per2 mutant mice. Both retinal protein and mRNA expression of endothelial nitric oxide synthase were decreased by twofold. Other endothelial function genes (VEGFR2, VEGFR1) were downregulated (1.5–2-fold) in Per2 mutant retinas, whereas there was an upregulation of profibrotic pathway mediated by transforming growth factor-β1. Our studies suggest that Per2 mutant mice recapitulate key aspects of diabetes without the metabolic abnormalities, including retinal vascular damage, neuronal loss in the bone marrow, and diminished BMPC function.
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影响因子：
7.7
作者：
Caballero, Sergio;Sengupta, Nilanjana;Grant, Maria B.
通讯作者：
Grant, Maria B.
影响因子：
2.5
作者：
Ju, WK;Neufeld, AH
通讯作者：
Neufeld, AH
DOI：
10.1196/annals.1354.020
发表时间：
2006-01-01
期刊：
UNDERSTANDING AND MODULATING AGING
影响因子：
--
作者：
Neves, Delminda;Santos, Janete;Vendeira, Pedro
通讯作者：
Vendeira, Pedro
DOI：
10.1084/jem.20090889
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Busik JV;Tikhonenko M;Bhatwadekar A;Opreanu M;Yakubova N;Caballero S;Player D;Nakagawa T;Afzal A;Kielczewski J;Sochacki A;Hasty S;Li Calzi S;Kim S;Duclas SK;Segal MS;Guberski DL;Esselman WJ;Boulton ME;Grant MB
通讯作者：
Grant MB
影响因子：
5
作者：
Ayalasomayajula, SP;Kompella, UB
通讯作者：
Kompella, UB