Per2 Mutation Recapitulates the Vascular Phenotype of Diabetes in the Retina and Bone Marrow

• DOI: 10.2337/db12-0172
• Publication Date: 2012-11-29T01:46:44Z
• Authors: Ashay D. Bhatwadekar; Yuanqing Yan; Xiaoping Qi; Jeffrey S. Thinsc...; Matthew B. Neu; Sergio Li Calzi; Lynn C. Shaw; James M. Dominiguez; Julia V. Busik; Choogon Lee; Michael E. Boulton; Maria B. Grant
• Keywords: Complications; Diabetic Retinopathy; Nitric Oxide Synthase Type III; Period Circadian Proteins; Hematopoietic Stem Cells; Nitric Oxide; Vascular Endothelial Growth Factor Receptor-2; Permeability; Retina; Circadian Rhythm; Transforming Growth Factor beta1; Mice; Phenotype; Bone Marrow; Mutation; Diabetes Mellitus; Animals

In this study, we assessed whether Per2 clock gene-mutant mice exhibit a vascular phenotype similar to diabetes. (B6.129-Per2(tm1Drw)/J) or wild-type control 4 and 12 months of age were used. To evaluate diabetes-like in mutant mice, retina was quantified for mRNA expression, degree diabetic retinopathy evaluated. Bone marrow neuropathy studied by staining femurs tyrosine hydroxylase (TH) neurofilament 200 (NF-200). The rate proliferation quantification bone progenitor cells (BMPCs) performed, threefold decrease 50% reduction nitric oxide levels observed mice. TH-positive nerve processes NF-200 reduced Both retinal protein expression endothelial synthase decreased twofold. Other function genes (VEGFR2, VEGFR1) downregulated (1.5-2-fold) retinas, whereas there an upregulation profibrotic pathway mediated transforming growth factor-β1. Our studies suggest that recapitulate key aspects diabetes without the metabolic abnormalities, including damage, neuronal loss marrow, diminished BMPC function.