Canine leukocyte adhesion deficiency colony for investigation of novel hematopoietic therapies.
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.
Creevy
Kate E
KE
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.
Bauer
Thomas R
TR
Tuschong
Laura M
LM
Embree
Lisa J
LJ
Colenda
Lyn
L
Cogan
Kevin
K
Starost
Matthew F
MF
Haskins
Mark E
ME
Hickstein
Dennis D
DD
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
D018821:CD18 Antigens