Clinical+Correlation+for+Week+2.pdf

Clinical Correlation Gray-coated collie pup (photograph provided by Michelle Tennis) A genetic disorder of collies results in gray coat color and increased susceptibility to bacterial infections. Within eight to twelve weeks of age, affected puppies develop symptoms such as fever, diarrhea, joint pa...

Clinical Correlation Gray-coated collie pup (photograph provided by Michelle Tennis) A genetic disorder of collies results in gray coat color and increased susceptibility to bacterial infections. Within eight to twelve weeks of age, affected puppies develop symptoms such as fever, diarrhea, joint pain, respiratory and skin infections. Puppies often die before they reach six months of age. Every twelve to fifteen days, these puppies develop a marked neutropenia after which the number of circulating neutrophils rebounds. During these periods of neutropenia, the animals are extremely susceptible to bacterial infections that often result in illness and dramatically shortened lives. Challenge question Propose an explanation for the susceptibility to opportunistic bacterial infections in these puppies. Canine cyclic neutropenia mutation in the gene encoding the protein AP3β1 - responsible for normal trafficking of granular proteins (such as elastase) to cytoplasmic granules during certain stages in hematopoiesis. results in a cyclic arrest of maturation of myeloid progenitor cells in the bone marrow, hence compromised production of early myeloid cells. affects melanocytes (resulting in the gray coat color) and bone marrow stem cells leading to fluctuating number of neutrophils in blood circulation. neutrophils are one of the primary innate defenders against bacterial attack, their depletion in periods of neutropenia underpins the clinical presentation of recurrent bacterial infections. Management strategy Support myelopoiesis by increasing the concentration of the hematopoietic growth factor G-CSF through injection of exogenous GCSF or increasing the expression of G-CSF through gene therapy.