Maternal genotype influences behavioral development of 3×Tg-AD mouse pups

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Abstract

Transgenic mice are a valuable tool in the investigation of neurodegenerative disorders such as Alzheimer's disease. The triple transgenic mouse (3×Tg-AD) is a model of Alzheimer's disease that possesses age-related amyloid beta plaques, neurofibrillary tangles and cell death as well as cognitive decline. Because maternal effects may interact with pup genotype in determining behavior phenotypes, we used a cross-fostering paradigm to investigate the effects of maternal genotype on behavioral development of the 3×Tg-AD mouse model and its wildtype control (B6129S1F2) from 2 to 24 days of age. Developmental patterns of behavior were influenced by both pup and maternal genotype. The 3×Tg-AD mice were delayed in sensory reflexes, showed less activity and poorer habituation to a novel object, but showed advanced development of motor reflexes compared to wildtype pups. While there were no differences in levels of maternal care between transgenic and control mothers, maternal genotype affected the development of several pup reflexes (body weight, hindlimb grasp reflex, loss of crossed extensor reflex, vibrissae response, righting reflex) and the number of horizontal and vertical beam breaks in an open field. This study is the first to examine neurobehavioral development and maternal behavior in a mouse model of Alzheimer's disease, and highlights the importance of investigating the consequences of early environmental experience as well as genetic manipulation on behavioral development.

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