Huntington's disease (HD) is a
hereditary neurodegenerative disease caused by the expansion of a
polyglutamine stretch in the huntingtin (HTT)
protein and characterized by dysregulated
calcium homeostasis. We investigated whether these disturbances are correlated with changes in the
mRNA level of the genes that encode
proteins involved in
calcium homeostasis and signaling (i.e., the calciosome). Using custom-made TaqMan low-density arrays containing probes for 96 genes, we quantified
mRNA in the striatum in YAC128 mice, a model of HD, and wildtype mice. HTT mutation caused the increased expression of some components of the
calcium signalosome, including
calretinin,
presenilin 2, and calmyrin 1, and the increased expression of genes indirectly involved in
calcium homeostasis, such as huntingtin-associated
protein 1 and
calcyclin-
binding protein. To verify these findings in a different model, we used PC12 cells with an inducible expression of mutated full-length HTT. Using single-cell imaging with
Fura-2AM, we found that store-operated Ca(2+) entry but not endoplasmic reticulum (ER) store content was changed as a result of the expression of mutant HTT. Statistically significant downregulation of the Orai
calcium channel subunit 2,
calmodulin, and
septin 4 was detected in cells that expressed mutated HTT. Our data indicate that the dysregulation of
calcium homeostasis correlates with changes in the gene expression of members of the calciosome. These changes, however, differed in the two models of HD used in this study. Our results indicate that each HD model exhibits distinct features that may only partially resemble the human disease.