Splicing variants in sheep CLN3, the gene underlying juvenile neuronal ceroid lipofuscinosis

Mutations in different genes underlie different forms of the neuronal ceroi d lipofuscinoses (NCLs, Batten disease). Subunit c of mitochondrial ATP syn thase specifically accumulates in most of them, including the juvenile CLN3 form and a sheep form orthologous to CLN6. Products of these genes are lik ely to be components of a complex or pathway for subunit c turnover, and th eir expression may be cross-regulated. Different bands, some with different subcellular distributions, were detected by antisera against different reg ions of CLN3 on Western blots of sheep tissues. Affected liver blots were t he same as controls but a specific 50-kDa band was at higher concentration in affected brain homogenates than in controls. Others have also reported b ands reacting differently to different CLN3 antibodies. When the 3' end of sheep CLN3 cDNA was amplified by RT-PCR, four mRNA splicing variants were f ound. Different CLN3 splicing variants at the 5' end of the human cDNA have been reported. These mRNA splicing variants may account the variation of e pitope distribution and the different subcellular locations of the CLN3 gen e product(s). The predicted size of the unmodified CLN3 protein is 48 kDa. Significantly higher molecular weight bands may correspond to oligomers of a CLN3 isoform or to a CLN3 isoform tightly bound to another protein. (C) 1 999 Academic Press.