Microarray Analysis of the Effects of a γ-protein Kinase C Null Mutation on Gene Expression in Striatum: A Role for Transthyretin in Mutant Phenotypes

A constitutive null mutation of the neural-specific isotype of protein kinase C (γ-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that γ-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of γ-PKC gene deletion also may be due to altered gene expression. To examine alterations in gene expression, microarray analyses were performed on striatal tissue from wild types and mutants. A total of 143 genes and ESTs were identified as potential candidates related to differences between null mutants and wild types. Confirmation studies using qRT-PCR indicated that the expression of transthyretin was increased about 8-fold in striatum of naive mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because γ-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naive and control-diet treated mutants, but did not affect transthyretin expression in wild types.