Immunohistochemical study of the expression of exon11-containing mu opioid receptor variants in mouse brain.
The cloned mu 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.
Abbadie
C
C
Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, 275 York Avenue, New York, NY 10021, USA.
Pan
Y-X
YX
Pasternak
G W
GW
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009833:Olfactory Pathways / Q000166:cytology / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism
D020033:Protein Isoforms; D017450:Receptors, Opioid, mu; D004298:Dopamine