title: Canine leukocyte adhesion deficiency colony for investigation of novel hematopoietic therapies.
abstract: The genetic immunodeficiency disease canine leukocyte adhesion deficiency (CLAD) was originally described in juvenile Irish Setters with severe, recurrent bacterial infections. CLAD was subsequently shown to result from a mutation in the leukocyte integrin CD18 subunit which prevents leukocyte surface expression of the CD11/CD18 complex. We describe the development of a mixed-breed CLAD colony with clinical features that closely parallel those described in Irish Setters. We demonstrate that the early identification of CLAD heterozygotes and CLAD-affected dogs by a combination of flow cytometry and DNA sequencing allows the CLAD-affected animals to receive life-saving antibiotic therapy. The distinct clinical phenotype in CLAD, the ability to detect CD18 on the leukocyte surface by flow cytometry, and the history of the canine model in marrow transplantation, enable CLAD to serve as an attractive large-animal model for the investigation of novel hematopoietic stem cell and gene therapy strategies.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Rm 12C-116, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Creevy
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bauer
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tuschong
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Embree
authors.forename: Lyn
authors.initials: L
authors.lastname: Colenda
authors.forename: Kevin
authors.initials: K
authors.lastname: Cogan
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Starost
authors.forename: Mark E
authors.initials: ME
authors.lastname: Haskins
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000818:Animals; D001947:Breeding; D018821:CD18 Antigens / Q000032:analysis; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D004285:Dogs / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype
chemical_list: D018821:CD18 Antigens