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

Abstract

A constitutive null mutation of the neural-specific isotype of protein kinase C (gamma-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that gamma-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of gamma-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 naïve mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because gamma-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naïve and control-diet treated mutants, but did not affect transthyretin expression in wild types.

Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling

“…Furthermore, the similarities of DEGs (Prkcg, opioid signaling genes, Rassf5, potassium channel subunits, Lore QTL genes) and gene networks (MAPK signaling pathway, oligodendrocyte enrichment, Lore4 QTL enrichment) between this study and prior studies using other models of alcohol behaviors were noteworthy (Darlington et al 2013;Smith et al 2006). This led us to propose that wheel running induced an increase in sensitivity to ethanol, thereby decreasing ethanol consumption.…”

“…A previous study of gamma-protein kinase c ( Prkcg ) showed the differences in ethanol consumption between null mutant and wildtype mice could be correlated with differences in the expression of transthyretin ( Ttr ) (Smith et al, 2006). While we previously showed a similar difference in Ttr expression between strains of mice selected for ethanol sensitivity, the current study does not support this.…”

Transcriptome analysis of Inbred Long Sleep and Inbred Short Sleep mice

“…In addition to genes from Lore QTL regions, transthyretin (Ttr) on chromosome 19 was also identified in both samples as being differentially expressed. Gamma-protein kinase C (PKC-γ ) null mutant mice and their wild-types have similar ethanol-related behaviors as the ISS and ILS mice, and these differences were correlated with baseline Ttr expression, which is higher in mutant mice (Smith et al 2006). Similar to the ISS mice, PKC-γ null mutants are less sensitive to acute ethanol than their wild-type littermates (Harris et al 1995), and voluntarily consume more ethanol (Bowers & Wehner 2001).…”

Protein kinase C as a stress sensor

“…DNA microarray analyses on the PKCγ knockout mice show changes in activity towards transerythrin, a thyroxin and retinol transport protein [98]. In brain, PKCγ directly interacts with and phosphorylates the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit [100].…”