Barabas, Amanda J., Robbins, Lindsey A. and Gaskill, Brianna N. (2022) Home cage measures of Alzheimer's disease in the rTg4510 mouse model. Genes, Brain and Behavior, 21 (2). ISSN 1601-1848

Abstract

Alzheimer's disease affects an array of activities in patients' daily lives but measures
other than memory are rarely evaluated in animal models. Home cage behavior, however, may provide an opportunity to back translate a variety of measures seen in
human disease progression to animal models, providing external and face validity.
The aim of this study was to evaluate if home cage measures could indicate disease
in the rTg4510 mouse model. We hypothesized that sleep, nesting, and smell discrimination would be altered in mutant mice. Thirty-two transgenic mice were used in a
Latin square design of four genotypes x both sexes x two diets. Half the mice
received a doxycycline diet to suppress tauopathy and evaluate tau severity on various measures. At 8-, 12-, and 16-weeks old, 24 h activity/sleep patterns, nest complexity, and odor discrimination were measured. After 16-weeks, tau concentration
in the brain was quantified. Mutant mice had increased tau concentration in brain tissue, but it was reduced by the doxycycline diet. However, only nest complexity was
different between mutant mice and controls. Overall, tauopathy in rTg4510 mice
does seem to affect these commonly observed symptoms in human patients. However, while running this study, a report showed that the rTg4510 mutant phenotype
is not caused by the mutation itself, but confounding factors from transgene insertion. Combined with report findings and our data, the rTg4510 model may not be an
ideal model for all aspects of human Alzheimer's disease.

Item Type:	Article
Keywords:	Alzheimer's disease, animal behavior, back-translation, ethology, food grinding, mouse model, olfaction, preclinical model, rTg4510, tauopathy
Date Deposited:	04 Mar 2022 00:45
Last Modified:	04 Mar 2022 00:45
URI:	https://oak.novartis.com/id/eprint/46941