Investigating dog breed susceptibility to diabetes mellitus using stem cell-derived canine pancreatic beta cells

Professor Lucy Davison (primary)
Clinical Sciences and Services
Royal Veterinary College and University of Oxford
Dr Jay Dudhia (secondary)
Clinical Sciences and Services
Royal Veterinary College

Abstract

Samoyed dogs are highly susceptible to insulin deficiency diabetes, whereas Boxers are resistant. Our HYPOTHESIS is that breed differences in pancreatic beta cell biology impact on cell survival and regeneration. We aim to generate stem-cell derived beta cells from Samoyed and Boxer dogs to compare their gene expression profiles and to assess functional differences under different pathophysiological conditions. We will generate induced pluripotent stem cells and differentiate these to a beta cell phenotype. RNAseq will be performed to determine their transcriptomic profiles. Cells will be cultured under pathophysiological conditions and molecular pathways associated with apoptosis and proliferation interrogated.


References

O’Kell AL, Wasserfall C, Catchpole B, Davison LJ, Hess RS, Kushner JA, Atkinson MA. Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked? Diabetes. 2017 Jun;66(6):1443-1452.

Brevini TA, Pennarossa G, Acocella F, Brizzola S, Zenobi A, Gandolfi F. Epigenetic conversion of adult dog skin fibroblasts into insulin-secreting cells. Vet J. 2016 May;211:52-6.

Cryopreservation of canine cardiosphere-derived cells: Implications for clinical application. Dutton LC, Church SAV, Hodgkiss-Geere H, Catchpole B, Huggins A, Dudhia J, Connolly DJ. Cytometry A. 2018 Jan;93(1):115-124.

Holder AL, Kennedy LJ, Ollier WE, Catchpole B. Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes. Vet Immunol Immunopathol. 2015 Oct 15;167(3-4):130-8.


BBSRC Area
Animal disease, health and welfare
Area of Biology
Cell BiologyDevelopment
Techniques & Approaches
BioinformaticsMolecular BiologySimulation / Modelling