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

Ashay 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

38 Citations (Scopus)

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 2013
Externally publishedYes

Fingerprint

Blood Vessels
Retina
Bone Marrow
Phenotype
Mutation
Tyrosine 3-Monooxygenase
Bone Marrow Cells
Stem Cells
Staining and Labeling
Retinal Vessels
Messenger RNA
Nitric Oxide Synthase Type III
Diabetic Retinopathy
Femur
Genes
Nitric Oxide
Up-Regulation
Down-Regulation
Growth
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Bhatwadekar, A., Yan, Y., Qi, X., Thinschmidt, J. S., Neu, M. B., Li Calzi, S., ... 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

Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow. / Bhatwadekar, Ashay; Yan, Yuanqing; Qi, Xiaoping; Thinschmidt, Jeffrey S.; Neu, Matthew B.; Li Calzi, Sergio; Shaw, Lynn C.; Dominiguez, James M.; Busik, Julia V.; Lee, Choogon; Boulton, Michael E.; Grant, Maria B.

In: Diabetes, Vol. 62, No. 1, 01.2013, p. 273-282.

Research output: Contribution to journalArticle

Bhatwadekar, A, Yan, Y, Qi, X, Thinschmidt, JS, Neu, MB, Li Calzi, S, Shaw, LC, Dominiguez, JM, Busik, JV, Lee, C, Boulton, ME & Grant, MB 2013, 'Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow', Diabetes, vol. 62, no. 1, pp. 273-282. https://doi.org/10.2337/db12-0172
Bhatwadekar, Ashay ; Yan, Yuanqing ; Qi, Xiaoping ; Thinschmidt, Jeffrey S. ; Neu, Matthew B. ; Li Calzi, Sergio ; Shaw, Lynn C. ; Dominiguez, James M. ; Busik, Julia V. ; Lee, Choogon ; Boulton, Michael E. ; Grant, Maria B. / Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow. In: Diabetes. 2013 ; Vol. 62, No. 1. pp. 273-282.
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