Functional analysis of alternatively spliced transcripts of the human histidine decarboxylase gene and its expression in human tissues and basophilic leukemia cells

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Abstract
L‐Histidine decarboxylase (HisDC) is the enzyme catalyzing the formation of histamine from L‐histidine. HisDC activity is expressed specifically in mast cells/basophils, endocrine cells in stomach, and histaminergic neurons in brain. As a first step in the analysis of the regulation of HisDC gene expression, we have cloned the cDNA coding for HisDC from a cDNA library of a human basophilic leukemia cell line, KU‐812‐F. We identified two types of HisDC cDNA, representing the 2.4‐kb and 3.4‐kb HisDC mRNA constitutively expressed in these cells. Sequence analysis of these cDNA revealed that the 3.4‐kb mRNA contains the insert sequence of 824 bases and suggests that both 2.4‐kb and 3.4‐kb mRNA may represent the alternatively spliced transcripts of the HisDC gene. Using expression plasmids containing a cDNA for each HisDC mRNA, we analyzed the function of possible HisDC isoforms. We show that only the 2.4‐kb mRNA encodes functional HisDC and is expressed in human brain and lung. However, we were unable to detect the 3.4‐kb mRNA in these tissues. Thus, the 3.4‐kb mRNA may be generated by KU‐812‐F cell‐specific splicing of the HisDC gene transcripts. Furthermore, we demonstrated the increase in the level of 2.4‐kb HisDC mRNA and HisDC activity in KU‐812‐F cells following treatment with phorbol 12‐myristate 13‐acetate.