title: Increased expression of P/Q-type Ca2+ channel alpha1A subunit mRNA in cerebellum of N-type Ca2+ channel alpha1B subunit gene-deficient mice.
abstract: The Ca(2+) channel alpha(1B) subunit is a pore-forming component capable of generating N-type Ca(2+) channel activity. Although the N-type Ca(2+) channel plays a role in a variety of neuronal functions, alpha(1B)-deficient mice show normal behavior, presumably owing to compensation by the other Ca(2+) channels. In this study, we examined the mRNA expression of the P/Q-type Ca(2+) channel alpha(1A) subunit in cerebellum of alpha(1B)-deficient mice. The alpha(1A) subunit mRNA in homozygous alpha(1B)-deficient mice was expressed at a significantly higher level than in wild or heterozygous mice. To examine whether the increased expression is induced by a cis-regulatory element within the 5'-upstream region of the alpha(1A) subunit gene, we examined lacZ expression in alpha(1B)-deficient x alpha(1A)3.0-lacZ mice (carrying a 3.0-kb 5'-upstream fragment of the alpha(1A) subunit gene fused to Escherichia coli lacZ reporter gene), which express lacZ in granule but not in Purkinje cells, and in alpha(1B)-deficient x alpha(1A)6.3-lacZ mice (carrying a 6.3-kb 5'-upstream region fused to lacZ gene), which express lacZ in Purkinje but not in granule cells. The levels of lacZ expression in homozygous alpha(1B)-deficient x alpha(1A)3.0-lacZ mice were significantly higher than in wild or heterozygous mice, but no difference in lacZ expression level was found among wild, heterozygous and homozygous alpha(1B)-deficient x alpha(1A)6.3-lacZ mice. Therefore, a possible explanation of the normal behavior of alpha(1B)-deficient mice is that compensation by alpha(1A) subunit gene occurs and that the 3.0-kb 5'-upstream region of alpha(1A) subunit gene contains an enhancer cis-element(s) for compensation in cerebellar granule cells.
authors.affiliation: Tsukuba Research Laboratory, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. e2-takahashi@hhc.eisai.co.jp
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ino
authors.forename: Norimasa
authors.initials: N
authors.lastname: Miyamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagasu
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D020864:Calcium Channels, N-Type / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D007763:Lac Operon / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D021122:Protein Subunits; D012333:RNA, Messenger; D001616:beta-Galactosidase