DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs.

Abstract

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.

• Authors: J L Wagner, R Storb, B Storer, E Mignot
• Journal: Tissue antigens (Tissue Antigens) Vol. 56 Issue 3 Pg. 223-31 (Sep 2000) ISSN: 0001-2815 [Print] England
• PMID: 11034558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• Histocompatibility Antigens Class I
• Orexin Receptors
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide
• histocompatibility antigen DLA

Topics

• Animals
• Bone Marrow Transplantation
• Dog Diseases (genetics, immunology)
• Dogs
• Female
• Gene Frequency
• Genetic Linkage
• Genetic Predisposition to Disease
• HLA-DQ Antigens (genetics, immunology)
• HLA-DQ beta-Chains
• Histocompatibility Antigens Class I (genetics, immunology)
• Histocompatibility Testing
• Male
• Mutation
• Narcolepsy (genetics, immunology, veterinary)
• Orexin Receptors
• Pedigree
• Polymorphism, Genetic
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide (genetics)