Immunohistochemical study of the expression of EXON11-containing μ opioid receptor variants in mouse brain

The cloned μ opioid receptor MOR-1 undergoes alternative splicing. Extensive 3′-splicing downstream from exon 3 leads to a number of C-terminal splice variants that are differentially expressed within the CNS. Recently, 5′-splicing has been observed with eight additional variants containing exon 11, a new exon located approximately 10 kb upstream from exon 1 that is under the control of a different promoter located even further upstream. Three of these variants generate the same protein as MOR-1 itself, but under the control of the new exon 11 promoter. Three variants in which exon 11 is translated have been identified within the brain, including MOR-1G, MOR-1M and MOR-1N. The present paper defines immunohistochemically the distribution of these variants using an exon 11-specific antiserum. The expression of exon 11-like immunoreactivity (-LI) was seen primarily in the olfactory tubercle, caudate-putamen, globus pallidus and substantia nigra. We did not observe exon 11-LI in a number of regions expressing MOR-1. Within the caudate-putamen, the general pattern of labeling was diffuse, in contrast to the pattern seen with an exon 4-generated antiserum that labels MOR-1 itself. However, we did observe in the caudate-putamen co-expression of exon 4- and exon 11-LI in cells that were apposed to dopaminergic terminals. These results provide new insights regarding the potential physiological significance of these exon 11-containing variants.