Investigation Into Possible Mutations of the SPINK1 Gene as a Cause of Hereditary Pancreatitis in the Miniature Schnauzer

The Miniature Schnauzer has been anecdotally reported to have a hereditary predisposition to the development of pancreatitis. The aims of this study were to establish a true breed predisposition for the disease and to investigate a potential genetic etiology. The first part of this study investigated breed predisposition for the development of pancreatitis. Miniature Schnauzers were found to have an odds ratio of 1.23 (P = 0.0240) for having an increased cPLI (as measured by an in-house ELISA or by Spec cPL®) serum concentration compared to the population as a whole. The second part of this study investigated the SPINK1 gene in Miniature Schnauzers with and without evidence of pancreatitis. Three variants were found in the gene and Miniature Schnauzers that were homozygous for the variants had an odds ratio of 25 (P = 0.0067) for having clinical and biochemical evidence of pancreatitis compared to healthy individuals. The third part of the study examined the entire canine genome using SNP scanning to investigate other genes or regions that may be associated with pancreatitis in the Miniature Schnauzer. The analysis revealed only a small region on chromosome 2 that was associated with the phenotype of pancreatitis. The SPINK1 gene is also located in this region. The final part of the study attempted to determine if one of the variants found in the second part of the study altered the final cDNA transcript. mRNA was extracted from the pancreas of Miniature Schnauzers known to have the variants and their cDNA was transcribed. It was found that this variant did not lead to exon skipping or truncation of the final protein transcript. In conclusion, this study demonstrated an increased prevalence of the phenotype of pancreatitis in the Miniature Schnauzer and was able to statistically associate this phenotype with variants in the SPINK1 gene. Further investigation into the mechanisms that may alter the structure, function, and expression of the SPINK1 variants found are warranted