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Feline Asthma

 

Feline Health

The College of Veterinary Medicine at Michigan State University has long been a leader in the fields of applied and basic airway research, and has developed a strong research focus group to investigate the genetic and molecular mechanisms of veterinary diseases. The college has identified feline health as a high priority clinical and research focus and is establishing the Pat Carrigan Chair in Feline Health to oversee the Center for Feline Health and Well-Being. By investigating the genetic mechanisms of feline asthma, an important chronic airway disease in the cat, our project serves to combine the college’s current expertise in airway research and molecular medicine with the long term goal of excellence in feline medicine.

 

Feline Asthma

Feline asthma is a common and serious problem in the cat that is well recognized in the veterinary literature. The asthmatic cat typically generates an inappropriate inflammatory airway response following exposure to allergens, while non-asthmatic cats are unaffected. Asthmatic cats have symptoms of cough, wheeze, labored breathing, and potentially life-threatening bronchoconstriction. The diagnostic hallmarks of feline asthma include recurrent airway obstruction, eosinophilic airway inflammation, and bronchial hyperresponsiveness. The genetic mechanisms that contribute to asthma in cats are unknown. This disease is very frustrating for clinicians and cat owners as it is chronic, the mechanism is unknown, and the treatment is palliative. Thus, our long-term objectives are to understand the mechanisms of feline asthma. Many studies provide evidence for a genetic predisposition to asthma in humans and in animal models of asthma and there is abundant anecdotal information in the veterinary literature to suggest that feline asthma may be inherited as well. We hypothesize that feline asthma has a hereditary basis.

 

Relationship to Other Species

Recurrent airway obstruction, eosinophilic airway inflammation, and bronchial hyperresponsiveness seen in feline asthma are also recognized in human asthmatics and can be experimentally induced in experimental models. The pathogenesis of asthma has been extensively studied in humans and murine models, and it is generally accepted that a genetic predisposition to asthma occurs in many families and exposure to environmental factors (allergens) is required for the development of clinical signs. Along with the strong evidence for the inheritance of asthma in humans and mice, there is abundant anecdotal information in the veterinary literature to suggest that feline asthma may be inherited as well. Much progress has been made towards identifying genes important in human asthma and in laboratory animal models of asthma. Because there is extensive homology in DNA sequence between species and the molecular mechanisms of human and feline asthma are anticipated to be similar based on the close similarity of their phenotypes, we anticipate that the work done in other species will greatly expedite the process of investigating the genetic mechanisms of asthma in the cat.

 

Our Research Goals

The goal of the current project is to assemble the tools required to perform linkage analyses in feline asthma. Linkage analysis is a statistical method of comparing the rate of inheritance of a known segment of DNA with the rate of inheritance of a phenotype, in this case asthma. In order to trace the inheritance of a phenotype, genetic markers must first be identified that vary between affected and unaffected individuals. Markers are defined as genetic sequences that assume different forms (termed "variable") in different individuals, such that the DNA sequence of a marker in an individual can be traced through either maternal or paternal origin for several generations. This is compared to the maternal or paternal origin of the asthma phenotype, and when there is a high rate of "coinheritance" of marker sequence and presence of asthma through the lineage of one parent, the traits are said to be "linked". Linkage information is valuable in that it supports nearby genes as potentially contributing to the asthma phenotype and excludes unlinked genes from having a direct affect on asthma. Candidate genes are genes that can be logically hypothesized to contribute to the phenotype under study on the basis of disease mechanisms. O’Brien and colleagues have identified over 350 feline (Felis catus) gene sequences and some of these may surround candidate genes and thus be valuable as DNA markers in our study.   

 

Summary

The overall goal of our feline asthma project is to identify genetic mechanisms that contribute to asthma in the cat. We are pursuing three objectives to complete this goal:

We are investigating the mode of inheritance of feline asthma by segregation analysis studies.

We are analyzing candidate genes and identify variable sequences within or near candidate genes to be used as markers for coinheritance studies.

In future studies we plan to combine the results from studies 1 and 2 and perform linkage analysis between the inheritance of feline asthma and informative DNA sequences within or near asthma candidate genes.

These methods require blood samples from the subjects and do not involve sacrifice or significant discomfort.  With these analysis we will be able to support or exclude genes from contributing to the asthma phenotype in cats and therefore better understand the mechanisms of this important feline disease. 

 

Principle Investigator: Susan Ewart, DVM, PhD

Co-Investigators: N. Bari Olivier, DVM, PhD, Michigan State University, East Lansing, MI

 

Related Links

Winn Feline Foundation - an organization dedicated to feline health

Pat Carrigan Chair in Feline Health - Michigan State University's feline health organization

Cat Fancier - Cat Fancier online

 

Related publications

Menotti-Raymond M, David VA, Lyons LA, et al. A genetic linkage map of microsatellites in the domestic cat (felis catus). Genomics 1999 57(9):9-23.

O'Brien SJ, Wienberg J, Lyons LA. Comparative genomics: lessons from cats. TIG 1997; 13(10):393-399.

O'Brien SJ, Cevario SJ, MArtenson JS, et al. Comparative gene mapping in the domestic cat (felis catus). J Hered 1997;88(5):408-414.

Dye JA, McKiernan B, Rozanski EA, et al. Bronchopulmonary disease in the cat. Historical, physical, radiographic, clinicopathologic and pulmonary function evaluation of 24 diseased and 15 healthy subjects. J Vet Intern Med 1996;10:385-400.

Padrid PA. Animal models of asthma. In: The Genetics of Asthma: Lung Biology in Health and Disease. Liggett SB, Meyers DA eds. Marcel Dekker, 1996, 211-233.

Corcoran BM, Foster DJ, Fuentes VL. Feline asthma syndrome: a retrospective study of athe clinical presentation in 29 cats. J Small Anim Pract 1995 Nov;36(11):481-488.

Dye J. Feline bronchopulmonary disease. Bet Clin N Am Small Anim Pract 1992, 22:1187-201.

Padrid PA. Chronic lower airway disease in the dog and cat. In: Problems in Veterinary Medicine. Spaulding GL ed. Lippincott, Piladelphia, 1992, 4:320-345.

Moise NS, Weidenkeller D, Yeager AE, Blue JT, Scarlett J. Clinical, radiographic, and bronchial cytologic features of cats with bronchial disease: 65 cases (1980-1986). J Am Vet Med Assoc 1989, 194:1476-1473

 

Funding Sources

Ewart SL. Candidate gene marker development for feline asthma. Companion Animal Fund, College of Veterinary Medicine, Michigan State University.