For those interested, this is the published abstract relating to the discovery of a gene for muscular dystrophy in cavaliers, referred to in a letter in a vet journal in the UK asking vets to help contribute to a better understanding on incidence.
As noted in the abstract, the gene has been identified in (only) three other breeds (all named) and in each breed, different genes are involved. This work is seen as important for understanding the affliction generally in dogs as well as humans. As with ongoing SM genome work, these are researchers hoping to benefit both dogs and human sufferers. By singling out a specific breed (the cavalier) for gene sequencing in this way, researchers believe humans may have a direct therapy benefit for a terrible, disabling disease that was not available from the results obtained from the other three breeds done. : -) I am certainly glad this work is being done on cavaliers -- as can be seen by the mix of US and UK researchers, as well as vet and human researchers (UC San Diego med school and the University College London Institute of Child Health -- I hope this reassures people that no one is targetting cavaliers to make them less appealing.
If people are concerned that too much research work is being done on cavalier health problems compared to other breeds, I encourage anyone to use one of the online scholarly publication databases and do some searches on various breeds. Cavaliers actually return quite a small number of studies, almost all done on 2 conditions, MVD and SM in the past 10-15 years (and in many of the MVD andother studies, cavaliers are simply part of a large sample). Other breeds can return many times as many published health-related papers. Fortunately for many of those breeds, the research work has resulted in direct therapies, genetic tests, and knowledge that has let breeders breed away from the problem. Hopefully cavaliers will benefit likewise from past and ongoing research funded by clubs, institutes and individuals.
As noted in the abstract, the gene has been identified in (only) three other breeds (all named) and in each breed, different genes are involved. This work is seen as important for understanding the affliction generally in dogs as well as humans. As with ongoing SM genome work, these are researchers hoping to benefit both dogs and human sufferers. By singling out a specific breed (the cavalier) for gene sequencing in this way, researchers believe humans may have a direct therapy benefit for a terrible, disabling disease that was not available from the results obtained from the other three breeds done. : -) I am certainly glad this work is being done on cavaliers -- as can be seen by the mix of US and UK researchers, as well as vet and human researchers (UC San Diego med school and the University College London Institute of Child Health -- I hope this reassures people that no one is targetting cavaliers to make them less appealing.
If people are concerned that too much research work is being done on cavalier health problems compared to other breeds, I encourage anyone to use one of the online scholarly publication databases and do some searches on various breeds. Cavaliers actually return quite a small number of studies, almost all done on 2 conditions, MVD and SM in the past 10-15 years (and in many of the MVD andother studies, cavaliers are simply part of a large sample). Other breeds can return many times as many published health-related papers. Fortunately for many of those breeds, the research work has resulted in direct therapies, genetic tests, and knowledge that has let breeders breed away from the problem. Hopefully cavaliers will benefit likewise from past and ongoing research funded by clubs, institutes and individuals.
MUTATIONAL ANALYSIS OF DYSTROPHIN DEFICIENT MUSCULAR DYSTROPHY IN CAVALIER KING CHARLES SPANIELS. G. L. Walmsley1, V.Arechavala-Gomeza2, M. Fernandez-Fuente1,2, N. Nagel3, R. Stanley1, K. Chandler1, F. Muntoni2, G. D. Shelton4 and R.J. Piercy1,2 1. Department of Veterinary Clinical Sciences, Royal Veterinary College, London, UK; 2. Dubowitz Neuromuscular Centre, UCL Institute of Child Health London, UK; 3. Northdale Veterinary Practice, West Sussex, UK; 4.Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA.
Canine dystrophin-deficient muscular dystrophy, analogous to Duchenne muscular dystrophy of humans, is a severe inherited degenerative disorder of striated muscle. This debilitating and ultimately fatal condition results in a progressive destruction of skeletal and cardiac muscle due to mutations in the gene encoding dystrophin, a structural protein that links the contractile apparatus to the sarcolemma. The disorder is seen in several canine breeds but the genetic cause has only been reported in the Golden Retriever, German Short-haired Pointer and Rottweiler. Here we present the findings of clinical, histopathological and molecularcharacterisation of this condition in Cavalier King Charles Spaniels.A 10 month old male neutered client-owned Cavalier KingCharles Spaniel from the United Kingdom was presented witha chronic progressive history of lethargy, exercise intolerance and dysphagia. The dog was tetraparetic with poor skeletal muscle mass (body condition score = 2/9), reduced spinal reflexes, macroglossia and restricted jaw movement. Investigations documented a marked elevation in creatine kinase activity (33,695U/l; 61 – 394U/l) and electromyography revealed spontaneous activity indicative of a primary muscle disorder (complex repetitive discharges and pseudomyotonia). Dystrophin-deficient muscular dystrophy was diagnosed on the basis of skeletal muscle histopathology, immunohistochemistry and immunoblotting using monoclonal antibodies to the dystrophin rod and carboxy termini. Oligonucleotide primer pairs designed for RT-PCR to amplify overlapping regions of dystrophin cDNA identified, following sequencing, an exon deletion and a frame-shift not present in control cDNA, that is predicted to result in premature termination of the protein product. Sequencing the associated genomic DNA confirmed the causative (and novel) mutation. The ability of antisense oligonucleotide induced exon skipping to restore the reading frame was demonstrated in vitro in cultured myoblasts from the affected dog. Sequencing of amplified DNA from an additional Cavalier King Charles Spaniel with dystrophin-deficient muscular dystrophy from North America identified the same mutation. In conclusion, dystrophin deficient muscular dystrophy in the Cavalier King Charles Spaniel may provide an excellent model for Duchenne muscular dystrophy due to the potential application for trials of antisense oligonucleotide-mediated exon skipping – one of the more promising research directions for genetic therapy in this fatal disorder.