ABSTRACT
The genetic disease canine leukocyte adhesion deficiency (CLAD) is characterized by recurrent, severe bacterial infections, typically culminating in death by 6 months of age. CLAD is due to a mutation in the leukocyte integrin CD18 subunit, which prevents surface expression of the CD11/CD18 leukocyte integrin complex. We demonstrate that stable mixed donor:host hematopoietic chimerism, achieved by a non-myeloablative bone marrow transplant from a histocompatible littermate, reverses the disease phenotype in CLAD. Donor chimerism following the transplant was demonstrated both by flow cytometric detection of donor-derived CD18-positive leukocytes in the peripheral blood of the recipient, and by the demonstration of donor-derived DNA microsatellite repeats in the peripheral blood leukocytes of the recipient. These results indicate that mixed hematopoietic chimerism reverses the clinical phenotype in CLAD and represents a potential therapeutic approach for the human disease leukocyte adhesion deficiency.
Subject(s)
Dog Diseases/therapy , Hematopoietic Stem Cell Transplantation/veterinary , Leukocyte-Adhesion Deficiency Syndrome/veterinary , Transplantation Chimera/immunology , Animals , Antigens, CD34/immunology , CD11 Antigens/immunology , CD18 Antigens/immunology , DNA/chemistry , DNA/genetics , Dog Diseases/immunology , Dog Diseases/pathology , Dogs , Flow Cytometry/veterinary , Hematopoietic Stem Cell Transplantation/methods , Leukocyte Count/veterinary , Leukocyte-Adhesion Deficiency Syndrome/immunology , Leukocyte-Adhesion Deficiency Syndrome/pathology , Leukocyte-Adhesion Deficiency Syndrome/therapy , Polymerase Chain Reaction/veterinaryABSTRACT
Spinal deformities in farmed Atlantic salmon (Salmo salar) are often observed in intensive farming systems and result in production losses. Many putative factors have been implicated with the formation of spinal deformities in larger salmon. This condition has been described as broken back syndrome, curvy back disease, and short tails.
