Date of Graduation

2016

Document Type

Dissertation

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Agricultural and Resource Economics

Committee Chair

Jeryl C Jones

Committee Co-Chair

Jianbo Yao

Committee Member

Barbara J Meade

Committee Member

Raymond Raylman

Committee Member

Amy Welsh

Abstract

Lumbosacral stenosis (LS) is a structural narrowing of the spinal canal in the canine lumbosacral spine. Large-sized working and sporting dog breeds such as Labrador retrievers are predisposed for reasons that are incompletely understood. Early diagnosis is essential for maximizing the quality of life, and minimizing the likelihood of early retirement in working dogs. Lumbosacral stenosis is usually considered to be a condition associated with degenerative changes observed with normal aging, however presence of the disease in young and middle aged working dogs has also been reported. This leads to the probable theory that some dogs in large breeds like Labrador retrievers might be genetically pre-disposed to LS.;Radiographic screening is common practice for agencies that purchase, train, and use working dogs. Dogs with morphologic traits such as canine hip dysplasia, canine elbow dysplasia, and transitional lumbosacral vertebrae are commonly rejected. However radiographs are insensitive for detecting LS. Advanced imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI) and the current standard diagnostic tests for detection of LS. These modalities are considered to be complimentary, with each offering different strengths for visualization of bony and soft tissue structures. For working dogs, computed tomography offers advantages of greater availability and the faster scanning times that allow the use of reversible sedation. Qualitative CT phenotyping is a standard method for clinical diagnosis of LS in dogs. However, for research purposes, a method for quantitative phenotyping of LS would also be beneficial. There is a lack of published evidence for a consensus on any such quantitative CT phenotypic traits in humans or dogs. In the first study, we developed one such quantitative trait using CT imaging in a sample of 25 Labrador retrievers---fat area ratio or FAR (ratio of the vertebral canal fat area content in a transverse slice to the vertebral body area in the same transverse slice). This measurement was found to have good agreement with the standard qualitative assessment of LS (as made by a certified veterinary radiologist); and we propose that FAR can be used to quantify LS especially in a research capacity.;Lumbar spinal stenosis (LSS) is a human condition that is often considered to be orthologous to canine LS. Genetic studies in humans have shown promise in identification of possible genetic factors that might be associated with LSS. The predominant genetic approach for research in canine LS has been pedigree analysis especially in the German shepherds; but no genetic association studies have been reported in any breed. The second study of the project was an attempt at the investigation into the genetic characteristics of LS in Labrador retrievers. To do so we analyzed the exome of 8 young Labrador retrievers---4 positive for LS and 4 negative for LS, from a pool of 40 Labrador retrievers in the US military working dog (MWD) program. The FAR measurement (from previous retrospective study in 25 dogs) was used for quantitative phenotyping of the 40 dogs (as well as qualitative CT phenotyping); followed by the selection of 8 dogs best representing the extremes of the phenotype---LS affected and LS unaffected. We were able to identify 3 genes---TTR (Transthyretin), FOLR2 (Folate Receptor 2) and USP9X (Ubiquitin Specific Peptidase 9, X-linked)---that could possibly be associated with canine LS. However, follow-up analysis is necessary to determine the true nature of the relationship between these genes and LS in Labrador retrievers. These 3 genes could potentially be new "candidate genes" for canine LS---not just in Labrador retrievers but also in other affected breeds. Further studies are also needed to investigate the role of these candidate genes in human LSS. The inability of LS in getting detected by simple radiographs is a major disadvantage for the agencies that procure, train and employ working dogs like the military and transportation safety authority. This necessitates the identification of genetic marker/s of LS that could then possibly be developed into simple diagnostic tests. And if certain breeds are indeed genetically predisposed, these diagnostic tests could perhaps even become standard screening protocol during the acquisition of these dogs. Labrador retrievers are loyal, kind, and intelligent breed of dogs; with greatly versatile applications beneficial to humans. Even though other breeds are used as working dogs around the world, Labrador retrievers cannot be easily replaced and the demand for this breed has been steadily increasing. A possible genetic test that can identify genetic predisposition to LS in young Labrador retrievers that might become working dogs can significantly improve the procurement process. And if reasons behind early occurrence of LS were premature degenerative changes instead, early detection would mean preventative conditioning training protocols and better therapeutic treatments. (Abstract shortened by UMI.).

Download

Share

COinS