Capucin: A novel striatal marker down-regulated in rodent models of Huntington disease

Abstract

In an initial study, we compared quantitative transcriptome data across mouse brain territories using the serial analysis of gene expression method. Among the novel regional markers that we discovered, we focused on a striatum-enriched transcript with no available experimental cDNA sequence. Here, we report its cloning, gene structure, and detailed distribution in mouse brain. Quantitative RT-PCR and in situ hybridization demonstrated predominant expression in dorsolateral striatum. We therefore named it capucin for caudate-and putamen-enriched sequence. Mouse capucin is a 237-amino-acid protein, without any registered ortholog in mammalian species. It contains no recognizable motif other than two predicted carboxy-terminal transmembrane domains. When expressed in fusion with a fluorescent protein, it localized to the Golgi apparatus in two mammalian cell lines. Interestingly, we observed a significant down-regulation of capucin mRNA levels in two rodent models of Huntington disease, indicating a possible contribution to the pathogenesis of this disorder.

SynDIG1: An Activity-Regulated, AMPA- Receptor-Interacting Transmembrane Protein that Regulates Excitatory Synapse Development

“…Sequence similarity to SynDIG1 was observed for three genes in the mouse genome with the highest degree of identity within the second half of the protein, including the two hydrophobic segments (Figure S1). The only related protein in mouse that has been characterized is referred to as “capucin” to reflect its predominant expression in caudate and putamen of the dorsolateral striatum (de Chaldee et al, 2006). …”

“…Capucin localizes to the Golgi compartment in heterologous cells (de Chaldee et al, 2006). To determine if SynDIG1 also localizes to Golgi structures, the distribution of HA-SynDIG1 was analyzed in COS cells with immunocytochemistry.…”

“…Detailed biochemical studies will be necessary to address this possibility. Finally, Capucin is down-regulated prior to striatal cell death in rodent models of Huntington’s disease (de Chaldee et al, 2006), reminiscent of the observation that SynDIG1 is down-regulated prior to Purkinje cell death in Lc cerebellum (Diaz et al, 2002). Thus, it is tempting to speculate that synaptic defects might precede neuronal death in Huntington’s disease.…”

Transcriptional signatures in Huntington's disease

“…de Chaldee et al used Serial Analysis of Gene Expression (SAGE) to identify capucin (caudate-and putamen-enriched sequence) (de Chaldee et al, 2006). Capucin mRNA distribution exhibits a strikingly restricted pattern, detectable only in brain and, to a lesser extent, in testis, and essentially confined to the striatum.…”

Possible involvement of self-defense mechanisms in the preferential vulnerability of the striatum in Huntington's disease

“…Notably, lower capucin mRNA levels have been detected in the R6/1 transgenic mouse model of HD (Desplats et al, 2006), R6/2 and in primary cultures of rat striatal neurons expressing a mutant fragment of human Htt than in the corresponding controls (de Chaldee et al, 2006). However, in vivo experiments showed that capucin overexpression is not able to counterbalance mHtt-induced toxicity in the striatum in a lentiviral mouse model of HD (Galvan et al, 2012b).…”