SURVIVAL MOTOR-NEURON (SMN) PROTEIN IN RAT IS EXPRESSED AS DIFFERENT MOLECULAR-FORMS AND IS DEVELOPMENTALLY-REGULATED

Spinal muscular atrophy (SMA) is an autosomal recessive disease charac terized by a progressive degeneration of motoneurons in spinal cord an d brainstem. The telomeric copy of a duplicated gene termed survival m otor neuron (smn), which maps to chromosome 5q13, has been found to be deleted in most patients. The encoded gene product is a novel protein which recently has been shown to accumulate in specific nuclear organ elles (gemini of coiled bodies, GEMS), and to play a part in the forma tion of the spliceosome complex. We have cloned and sequenced the rat smn cDNA. Antibodies generated against an N-terminus peptide recognize d a main protein of 32 kDa in immunoblots of rat embryonic tissue extr acts. Minor bands of 35 kDa, 45 kDa and, in perinatal muscle, of 24 kD a were also specifically detected, indicating that SMN is expressed as different molecular forms. Subcellular fractionation indicated that t he 32 kDa form is mainly soluble, while the 35 kDa and 45 kDa products segregate to the microsomal-mitochondrial fraction. SMN protein is hi ghly regulated during development: expression is high in embryonic tis sues (central nervous system, muscle, lung and liver), and then progre ssively decreases to very low levels in most tissues of the adult. The demonstration of different molecular forms of SMN along with its deve lopmental regulation may help to understand the contribution of this p rotein in the appearance of SMA phenotype.