Promoter analysis of the human centromeric and telomeric survival motor neuron genes (SMNC and SMNT)

Proximal spinal muscular atrophy (SMA) is caused by mutations in the telome ric (SMNT), but not centromeric (SMNC), survival motor neuron gene. Here we have identified and analyzed the two SMN promoters. We show that a 750-bp 5'-flanking fragment from each is capable of driving expression from a repo rter construct. Within this fragment, we define a similar to 200-bp element that results in high expression in a motor neuron cell line. Sequence comp arison of a 3.4-kb upstream fragment from each gene shows minimal differenc es. Although these differences produce a 2-fold difference in reporter acti vity between the two promoters, this is not sufficiently high to explain wh y SMNT, but not SMNC, is the disease determining gene. Our data thus demons trate, for the first time, almost complete equivalence between the SMN prom oters and rule out the important possibility that differences in them might explain why mutations in only the telomeric SMN gene cause SMA. (C) 1999 E lsevier Science B.V. All rights reserved.