ε-sarcoglycan immunoreactivity and mRNA expression in mouse brain

Myoclonus dystonia (M-D) is a hereditary movement disorder caused by a maternally imprinted gene that is often associated with psychiatric symptoms. Most cases of M-D are believed to result from mutations of the ε-sarcoglycan protein. The neuroanatomical distribution of ε-sarcoglycan-like immunoreactivity in mouse was investigated by using an anti-serum against the ε-sarcoglycan protein. The expression of ε-sarcoglycan mRNA was studied by a sensitive fluorescence in situ hybridization (FISH) method. Immunohistochemistry and FISH revealed a wide distribution of ε-sarcoglycan protein and mRNA throughout the mouse brain. High expression levels of ε-sarcoglycan mRNA and immunoreactivity were found in the mitral cell layer of the olfactory bulb, the Purkinje cell layer in cerebellum, and the monoaminergic neurons in the mouse midbrain. Immunohistochemistry revealed a similar distribution of ε-sarcoglycan protein. Double-labeling FISH showed colocalization of tyrosine hydroxylase and ε-sarcoglycan mRNAs within all the midbrain dopaminergic (DAergic) cell groups. By combining FISH with fluorescence immunohistochemistry, coexpression of ε-sarcoglycan mRNA and tryptophan hydroxylase immunoreactivity was found in the serotonergic (5-HTergic) neurons within the dorsal raphe nucleus. The distribution of ε-sarcoglycan in the mouse brain suggests that the symptom complex of M-D may be related to the effects of decreased ε-sarcoglycan activity on the development or function of monoaminergic neurons.