In the alternative splicing, intron retention, of histamine H(3) receptors in 
rats and mice, the short transcript isoforms that are excised alternatively 
spliced introns are easily detected in a very low level in rats and are 
undetectable in mice using the regular PCR protocol. The retained introns have 
common 5' splice site and different 3' splice sites. The detailed mechanism for 
the special alternative splicing remains largely unclear. In this study, we 
developed a minigene splicing system to recapitulate natural alternative 
splicing of the receptors and investigated the effects of 5' and 3' splice sites 
on intron retention in HeLa cells. Mutating weak 5' and 3' splice sites of the 
alternatively spliced introns toward the canonical consensus sequences promoted 
the splicing of the corresponding introns in rat and mouse minigenes. The effect 
of splice site strength was context-dependent and much more significant for the 
3' splice site of the longer alternative intron than for the 3' splice site of 
the shorter alternative intron and the common 5' splice sites; it was also more 
significant in the rat minigene than in the mouse minigene. Mutating the 3' 
splice site of the longer alternative intron resulted in almost complete 
splicing of the intron and made the corresponding isoform to become the nearly 
exclusive transcript in the rat minigene.