Epigenetic Rearing Factors in a Genetic Model of Parkinson's Disease

Abstract

<p>In the Pitx3ak/2J mouse model of Parkinson's disease, midbrain dopaminergic neurons fail to differentiate in the substantia nigra par compacta (SNc). However, prior studies using this model have reported inconsistencies on behavioral tests of functional deficit expected in a Parkinson's disease model (Hwang et aI., 2005; Kas et aI., 2008). Because different breeding schemes were used by the various investigators, we hypothesize that epigenetic factors, such as rearing environment and maternal-offspring interactions, may be contributing to these inconsistencies. In order to test this hypothesis, Pitx3 heterozygous females were mated to homozygous males (3:1), producing litters with a ratio of 50:50 heterozygote to homozygote offspring. From litters born within a 24 hour period, all pups were cross-fostered to the dams in order to create 3 types of rearing environments: homogeneous mutant, homogeneous heterozygous control, and mixed mutant and control. Offspring from these three rearing conditions were tested behaviorally at 2 months of age (P60) as adults in an open field and a pole climb task. For most behaviors, there was a main effect of Rearing Condition between mice raised in litters of homogeneous versus mixed configuration. Furthermore, a 3way Genotype x Gender x Rearing Condition interaction was seen in the frequency of exploratory behaviors in the pole climb task, suggesting that male and female mice are differentially affected by the type of rearing condition for some behaviors. Together, these results demonstrate that differences typically attributed to genetics alone may also include epigenetic factors such as breeding schemes and litter configurations. Consideration of these epigenetic factors may be necessary when interpreting behavioral results from genetically altered mice.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>