Gene Cloning And Identification Of The Alternative Splicing Of The Rabbit Histamine H3 Receptor

Alternative splicing mechanisms of RNA allow individual genes to produce multiple protein isoforms—thereby playing a central part in generating complex proteomes and becoming a widespreadly existing approach to increase the diversity of eukaryotic gene expression. At least 15%, and perhaps as many as 50%, of human genetic diseases arise from mutations either in consensus splice site sequences or in the more variable auxiliary elements known as exon and intron splicing enhancers and silencers. Alternative splicing may occur in the mRNA of the histamine H3 receptor. The H3 receptor cDNAs of the guinea pig, rat, mouse, monkey and hamster have been cloned and sequenced one after another since Lovenberg et al cloned the human H3 receptor cDNA in 1999, and alternative splicing was found in the human, guinea pig, rat, mouse and hamster, however, it was not found in the monkey, and no report about the rabbit can be available. The H3 receptor is known to modulate the synthesis and release of various neurotransmitters including histamine, acetylcholine, glutamate, dopamine, 5-hydroxytryptamine (serotonin) and norepinephrine in the brain. H3 receptors have been implicated in a variety of brain functions, including arousal, locomotor activity, thermoregulation, food intake, learning and memory, resulting in an intense interest in the H3 receptor for potential therapeutic exploitation for the treatment of sleep disorders, obesity, asthma, heart disease, migraine, epilepsy, as well as cognitive deficits in Alzheimer's Disease, Attention Deficit Hyperactivity...