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Pathobiology of canine cyclic hematopoiesis (review)
1Department of Pathobiology, University of Connecticut, Storrs 06268.
Insights
Canine cyclic hematopoiesis (CH) in Gray Collies mirrors human cyclic neutropenia (CN), featuring periodic blood cell fluctuations. This genetic disorder, linked to coat color, offers a vital model for understanding hematopoietic regulation and treating human CN.
Area of Science:
- Veterinary Medicine
- Genetics
- Hematology
Background:
- Canine cyclic hematopoiesis (CH), also known as lethal gray syndrome, is an inherited disorder in Gray Collies.
- CH is characterized by cyclical fluctuations in blood cell counts, particularly neutrophils, occurring at approximately 12-day intervals.
- This condition serves as a valuable animal model for human cyclic neutropenia (CN).
Purpose of the Study:
- To investigate the genetic basis and pathological mechanisms of canine cyclic hematopoiesis.
- To explore the parallels between canine cyclic hematopoiesis and human cyclic neutropenia.
- To highlight the utility of the Gray Collie model for studying hematopoietic regulation.
Main Methods:
- Phenotypic characterization of blood cell counts in affected Gray Collies.
- Genetic analysis to identify the causative gene and its linkage to coat color.
- Bone marrow transplantation studies to localize the hematopoietic defect.
Main Results:
- Canine cyclic hematopoiesis is an autosomal recessive disorder.
- The disease involves periodic neutropenia and other blood element changes, leading to increased susceptibility to infections.
- Bone marrow transplantation studies suggest the primary defect resides within the bone marrow, though the precise mechanism remains elusive.
Conclusions:
- Canine cyclic hematopoiesis is a critical genetic model for understanding cyclic neutropenia.
- The Gray Collie model provides insights into hematopoietic regulation and potential therapeutic strategies for human CN.
- Further research is needed to elucidate the exact molecular mechanisms underlying CH.
Abstract:
Canine cyclic hematopoiesis (CH) was first described in Gray Collies as the lethal gray syndrome, and was subsequently shown to be a counterpart of human cyclic neutropenia (CN). The disease is characterized by a recurrent cyclic change in the levels of neutrophils and other blood elements at approximately 12-day intervals. It is caused by an autosomally recessive gene with pleiotropic effects or a CH gene which is closely linked to a gray color gene. The infectious insult on affected animals is periodic but its clinical and pathologic effects are continual and cumulative Affected dogs die after weaning and rarely survive over 6 months of age. There is evidence of immunoregulatory defects in these dogs. Reciprocal bone marrow transplantation indicates that the defect resides in the bone marrow, but the actual site and mechanism of the defect has not been established. The disease in Gray Collies represents a unique model system for studying the mechanism of cyclic hematopoiesis and hematopoietic regulation. Studies of the disease have made conceptual contributions toward understanding and treatment of human cyclic neutropenia.