DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs.
Human narcolepsy is a neurological disorder known to be tightly associated with HLA-DQB1*0602. A clinically similar disorder has been described in various dog breeds. The canine form of the disease is inherited as an autosomal recessive disorder in Labrador retrievers and Doberman pinschers (canarc-1) but occurs sporadically in other breeds, most typically dachshunds and poodles. In this study, we have examined if there is a relationship between the development of narcolepsy and specific dog leukocyte antigen (DLA)-DQB1 alleles. Ninety-nine dogs were typed for DLA-DQB1-31 with narcolepsy and 68 control animals. Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of the hypocretin receptor 2 (Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA. Four Hcrtr2-positive families (two Doberman pinscher families, one Labrador retriever family, one dachshund family) were analyzed at the DLA-DQ level. No relationship was found between narcolepsy and DLA in Hcrtr2-mediated narcolepsy but loose genetic linkage was observed (Zmax=2.3 at theta=25%, m= 40). Bone marrow transplantation between two DLA identical affected (Hcrtr2-/-) and unaffected (Hcrtr2+/-) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers. DLA-DQB1 was next studied in 11 dogs with sporadic (non-familial) narcolepsy and in unrelated control animals of the same and different breeds. The allelic and carrier frequencies of various DLA-DQB1 alleles were analyzed. There was no strong positive or negative correlation between the development of narcolepsy and specific DLA-DQB1 alleles. These results do not support the involvement of DLA-DQ in canine narcolepsy, whether of sporadic or familial origin.
Wagner
J L
JL
Clinical Research Division, Fred Hutchinson Research Center, Seattle, Washington, USA.
Storb
R
R
Storer
B
B
Mignot
E
E
D000818:Animals; D016026:Bone Marrow Transplantation; D004283:Dog Diseases / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D008297:Male; D009154:Mutation; D009290:Narcolepsy / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D064446:Orexin Receptors; D010375:Pedigree; D011110:Polymorphism, Genetic; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000235:genetics
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015395:Histocompatibility Antigens Class I; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C039692:histocompatibility antigen DLA