Developing mouse models of aging: a consideration of strain differences inage-related behavioral and neural parameters

Increased interest is emerging for using mouse models to assess the genetic s of brain aging and age-related neurodegenerative diseases. Despite this d emand, relatively little information is available on aging in behavioral or neuromorphological parameters in various mouse strains that are being used to create transgenic and null mutant mice. We review several issues regard ing selection of appropriate strains as follows: (1) Does the behavioral pa rameter exhibit a significant age by strain interaction? (2) Do the strains differ in lifespan? (3) Are there potential intervening variables, such as strain specific performance strategies or disease, in the behavioral task being investigated that would confound the desired conclusions'! (4) Does t he behavioral difference have an underlying neural correlate? In this conte xt we present a conceptual model pertaining to the selection of mouse strai ns and behavioral parameters for genetic analyses. We also review the impor tance of applying stereological techniques for determining age-related stru ctural changes in the mouse brain as well as the potential value of a datab ase that would catalog this information. Thus, our intention is to undersco re the growing importance of mouse models of brain aging and the concomitan t need for additional information about mouse aging in general. (C) 1999 El sevier Science Inc, All rights reserved.