Lumbosacral stenosis in Labrador retriever military working dogs – an exomic exploratory study

Abstract

BackgroundCanine lumbosacral stenosis is defined as narrowing of the caudal lumbar and/or sacral vertebral canal. A risk factor for neurologic problems in many large sized breeds, lumbosacral stenosis can also cause early retirement in Labrador retriever military working dogs. Though vital for conservative management of the condition, early detection is complicated by the ambiguous nature of clinical signs of lumbosacral stenosis in stoic and high-drive Labrador retriever military working dogs. Though clinical diagnoses of lumbosacral stenosis using CT imaging are standard, they are usually not performed unless dogs present with clinical symptoms. Understanding the underlying genomic mechanisms would be beneficial in developing early detection methods for lumbosacral stenosis, which could prevent premature retirement in working dogs. The exomes of 8 young Labrador retriever military working dogs (4 affected and 4 unaffected by lumbosacral stenosis, phenotypically selected by CT image analyses from 40 dogs with no reported clinical signs of the condition) were sequenced to identify and annotate exonic variants between dogs negative and positive for lumbosacral stenosis.ResultsTwo-hundred and fifty-two variants were detected to be homozygous for the wild allele and either homozygous or heterozygous for the variant allele. Seventeen non-disruptive variants were detected that could affect protein effectiveness in 7 annotated (SCN1B, RGS9BP, ASXL3, TTR, LRRC16B, PTPRO, ZBBX) and 3 predicted genes (EEF1A1, DNAJA1, ZFX). No exonic variants were detected in any of the canine orthologues for human lumbar spinal stenosis candidate genes.ConclusionsTTR (transthyretin) gene could be a possible candidate for lumbosacral stenosis in Labrador retrievers based on previous human studies that have reported an association between human lumbar spinal stenosis and transthyretin protein amyloidosis. Other genes identified with exonic variants in this study but with no known published association with lumbosacral stenosis and/or lumbar spinal stenosis could also be candidate genes for future canine lumbosacral stenosis studies but their roles remain currently unknown. Human lumbar spinal stenosis candidate genes also cannot be ruled out as lumbosacral stenosis candidate genes. More definitive genetic investigations of this condition are needed before any genetic test for lumbosacral stenosis in Labrador retriever can be developed.Electronic supplementary materialThe online version of this article (10.1186/s40575-017-0052-6) contains supplementary material, which is available to authorized users.

Computed Tomographic Evaluation of the Sacroiliac Joints of Young Working Labrador Retrievers of Various Work Status Groups: Detected Lesions Vary Among the Different Groups and Finite Element Analyses of the Static Pelvis Yields Repeatable Measures of Sacroiliac Ligament Joint Strain

“…The study was a retrospective, secondary analysis, exploratory design. Labrador retriever working dogs, aged 11-48 months, that had undergone lumbosacral CT scanning for two, previous research studies were included (29,30). Due to the retrospective nature of the study, institutional animal care, and use committee approval was not required.…”

Computed Tomographic Measures of Funnel-Shaped Lumbar Vertebral Canal and Articular Process Dysplasia Malformations Differ Between German Shepherd and Belgian Malinois Military Working Dogs

“…One study identified a moderate to high heritability of several lumbosacral disease-related anatomical features in the lumbar spine in a large sample of German shepherds (34). Another study identified potential candidate genes for lumbosacral stenosis in a sample of 8 military working Labrador retrievers, and recommended that this candidate gene be further evaluated in larger samples and other breeds (35). Repeating the present study with a larger sample size of dogs would allow a "normal" vs. "affected" population to be established.…”

Canine Breeds Predisposed to Develop Diskospondylitis: A Retrospective Study of 181 Cases (2009-2018)

“…Labradors are a very popular household pet dog breed and one of the most common breeds used worldwide as working dogs. Recently studies demonstrated that this breed also has a genetic predisposition to similar diseases to DS such as lumbosacral stenosis (MUKHERJEE et al, 2017) and osteoarthritis (ANDERSON et al, 2018). Other hypothesis that may explain the high prevalence includes the genetic predisposition to obesity (MANKOWSKA et al, 2017).…”

“…Similarly to humans dog obesity can predispose or exacerbate several clinical conditions such as osteoarthritis, respiratory airway distress, renal diseases, diabetes mellitus and metabolic derangements (IMPELLIZERI et al, 2000;TVARIJONAVICIUTE et al, 2013). Notably both over-nutrition and obesity have been associated with impaired immunity and chronic low-grade inflammation in humans and mouse models (NIEMAN et al, 1999;BERG & SCHERER, 2005). In fact, Anderson et al (2018) reports that breeds at or above mean breed bodyweight were 2.3 times more likely to have osteoarthritis than dogs below average weight.…”