Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow

Ashay D. Bhatwadekar, Yuanqing Yan, Xiaoping Qi, Jeffrey S. Thinschmidt, Matthew B. Neu, Sergio Li Calzi, Lynn C. Shaw, James M. Dominiguez, Julia V. Busik, Choogon Lee, Michael E. Boulton, Maria B. Grant

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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 factorb1. 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.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalDiabetes
Volume62
Issue number1
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Bhatwadekar, A. D., Yan, Y., Qi, X., Thinschmidt, J. S., Neu, M. B., Li Calzi, S., Shaw, L. C., Dominiguez, J. M., Busik, J. V., Lee, C., Boulton, M. E., & Grant, M. B. (2013). Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow. Diabetes, 62(1), 273-282. https://doi.org/10.2337/db12-0172