E. A. Thorndike and A. S. Turner

Department of Clinical Sciences, Colorado State University, Ft.Collins ,CO 80523

Received 9/25/97 Accepted 4/10/98

2. GENERAL INTRODUCTION TO ANIMAL MODELS

To clarify the etiology and improve the management of certain diseases experienced by women after menopause, it is necessary to establish a suitable animal model to validate safety and efficacy of therapy. Previously, researchers have used non-human primates, dogs, cats, rabbits, guinea pigs, pigs, and minipigs, each of which these animal models possesses certain advantages and disadvantages (1). (table 1) In order to select an appropriate animal model for a given study, the investigator must take into consideration a wide variety of factors: 1) appropriateness as a model for estrogen deficiency , 2) genetic homogeneity of organism, 3) background knowledge of biological properties, 4) cost and availability, 5) ease of experimental manipulation, 6) ecological considerations, and 7) ethical and societal implications (1). It is of great importance that the model selected does not add too many new variables to an already complex problem (2); therefore, Ideally, the model chosen should closely mimic human diseases in its induction, progression, and pathology"(2). Obviously, no animal model can meet every criterion. In real life, compromises must be made and the best possible model is selected (1). This article will demonstrate that the sheep is a practical and highly suitable large animal model, for human postmenopausal diseases.

The sheep, more specifically the skeletally mature (> 3.5 yrs) or aged (>7 yrs.) ewe, is gaining recognition as a cost-effective large animal model for studying four of the most important postmenopausal diseases: CAD, osteoporosis, OA, and oral bone loss. This animal model can be used for studies directed at clarifying the details of pathogenesis that remain obscure, and it also can meet the criteria needed to test new therapeutic strategies that could help to prevent these diseases (3).

The sheep as an experimental animal model possesses numerous advantages. Although larger than many research animals, sheep are docile, compliant, and therefore easy to handle and house. Because sheep are raised in flocks, they experience little stress when they are housed in groups of two or more. For most people, there is less emotional attachment to sheep as compared to companion animals such as cats and dogs, which eases some of the ethical stigma associated with animal research (1). In an era of spiralling research costs, one clear advantage of using sheep as a large animal model is their relatively low maintenance costs (table 1). Finally, sheep are available in large numbers of "homogeneous populations" of known age, making them ideal for large scale studies (1).