SPONTANEOUS CANINE INSULINOMA: LESSONS IN DIABETES PREVENTION FROM IMMORTAL PANCREATIC BETA CELLS

Prof Lucy Davison (primary)
Clinical Sciences and Service
Royal Veterinary College
Prof Brian Catchpole (secondary)
Pathology and Pathobiology
Royal Veterinary College

Abstract

Canine insulinoma is a functional tumour of insulin-producing pancreatic beta cells. Whilst the condition is rare, certain dog breeds such as the Boxer, German Shepherd and Golden Retriever appear to be predisposed. Intriguingly, these insulinoma-prone breeds are protected from diabetes mellitus, a condition resulting from beta cell destruction. This suggests there are genetically-driven breed-related differences in beta cell health and survival among dog breeds. This project will use whole genome sequencing to explore genetic predisposition to canine insulinoma. In addition, single cell transcriptomics and immuno-histochemistry will be used to identify novel molecular drivers of beta cell survival and renewal.


References

1 Catchpole B, Ristic JM, Fleeman LM, Davison LJ. Canine diabetes mellitus: can old dogs teach us new tricks? Diabetologia. 2005 Oct;48- 10 -:1948-56. Epub 2005 Sep 8. Review. PubMed PMID: 16151773.
2 Catchpole B, Kennedy LJ, Davison LJ, Ollier WE. Canine diabetes mellitus: from phenotype to genotype. J Small Anim Pract. 2008 Jan;49- 1 -:4-10. Epub 2007 Jul 6. Review. PubMed PMID: 17617163.
3 Buishand FO, Visser J, Kik M, Gröne A, Keesler RI, Briaire-de Bruijn IH, Kirpensteijn J. Evaluation of prognostic indicators using validated canine insulinoma tissue microarrays. Vet J. 2014 Jul;201- 1 -:57-63. doi: 10.1016/j.tvjl.2014.05.004. Epub 2014 May 6. PubMed PMID: 24878267.
4 Schermerhorn T. Canine insulinoma as a model for studying molecular genetics of tumorigenesis and metastasis. Vet J. 2013 Aug;197- 2 -:126-7. doi: 10.1016/j.tvjl.2013.04.017. Epub 2013 May 23. PubMed PMID: 23707578
5 Buishand FO, Kirpensteijn J, Jaarsma AA, Speel EJ, Kik M, Mol JA. Gene expression profiling of primary canine insulinomas and their metastases. Vet J. 2013 Aug;197- 2 -:192-7. doi: 10.1016/j.tvjl.2013.01.021. Epub 2013 Feb 18. PubMed PMID: 23428643.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Genetics
Techniques & Approaches
BioinformaticsGeneticsMolecular Biology