Chapter

Large Animal Models

D.N. Palmer, I. Tammen, C. Drögemüller, G.S. Johnson, M.L. Katz and F. Lingaas

in The Neuronal Ceroid Lipofuscinoses (Batten Disease)

Second edition

Published on behalf of Oxford University Press

Published in print March 2011 | ISBN: 9780199590018
Published online November 2012 | e-ISBN: 9780191753459 | DOI: http://dx.doi.org/10.1093/med/9780199590018.003.0018

Series: Contemporary Neurology Series

Large Animal Models

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Since the report of ‘lipid dystrophic changes’ in two English Setter dogs (Hagen, 1953) an extensive literature has arisen reporting cases of NCL in a wide variety of animals, sufficient to suggest that these diseases are common to mammalian species. Cases have been reported in many different dog breeds, and in other species including sheep, cattle, ferrets, cats, horses, goats, pigs (Tables 18.1–18.4), and mice (see Chapter 17). nimal diseases have been described attributable to naturally occurring mutations in many of the NCL-causing genes.

The majority of these animal forms have been found in domesticated production and companion animals, inbred for consistency in production values, character, or appearance and thus susceptible to a strong founder effect. A strong interest in the genetic health status of these populations leads to a thorough veterinary diagnosis and considerable efforts to detect and manage any deleterious mutations. Diagnosis of NCLs in animals is of veterinary interest in its own right, particularly in animals valued as breeding stock or companions, but in many cases veterinary concerns are incidental compared to gains in knowledge of the analogous human diseases and the provision of an animal model to test therapies.

These model studies fall into two categories. A number of passive studies, mainly careful postmortem pathology investigations, have shaped our understanding of the general course of the neuropathology of the diseases. Such work in sheep allowed early molecular characterization of the storage material. This information becomes even more useful with time, as the genetic lesions are determined, allowing a more exact comparison to the human diseases.

Active studies utilize colonies containing affected animals deliberately bred and maintained for studies relevant to human disease. All affected animals in a colony have the same mutation and are closely interbred, so individual variations are small. Colonies derived from naturally occurring large domestic animal cases are particularly valuable because the brain size and structure is larger and more human-like than that of rodents. A longer life expectancy allows for investigation of long-term effects of treatments. In general, the clinical progression in larger animals more closely resembles that in humans and animal colonies are maintained free from drugs such as anti-epileptic agents.

Domestic production animals are economic to maintain, have been bred for easy management, and a high-level expertise in reproductive technology and veterinary care is available for them. With good early diagnosis or breeding programmes, experiments can begin at preclinical or early clinical disease, whereas human trials usually focus on the acutely affected patients. Most of the large animal cases reported have been in dogs or ruminants and large animal model studies have focused on these species.

This chapter is organized into sections describing the large animal models including sheep and cattle, with a separate section on dogs.

Chapter.  22654 words.  Illustrated.

Subjects: Neurology

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