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Ectopic expression of the bHLH gene Math1 disturbs neural development
Author(s) -
Isaka Fumiaki,
Ishibashi Makoto,
Taki Waro,
Hashimoto Nobuo,
Nakanishi Shigetada,
Kageyama Ryoichiro
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00699.x
Subject(s) - cre recombinase , ectopic expression , biology , transgene , microbiology and biotechnology , nervous system , neural stem cell , gene , genetically modified mouse , genetics , neuroscience , stem cell
The basic helix–loop–helix gene Math1, a positive regulator of neuronal differentiation, is specifically expressed in the dorsal part of the developing nervous system. To determine the effects of ectopic expression of Math1, we generated two transgenic mouse lines; One carried the Cre recombinase gene under the control of the nestin promoter and enhancer, which direct expression in neural precursor cells, and the other carried the Math1 gene, the expression of which was regulated by the cytomegalovirus (CMV) promoter but interrupted by the stop cassette flanked by loxP sites. In F1 embryos that carried the two transgenes, the stop cassette was removed by Cre recombinase in the developing nervous system, and Math1 expression was ectopically directed from the CMV promoter. We found that these embryos exhibited abnormal morphology of the brain and extensive cell death in the nervous system. These results suggest that ectopic expression of Math1 is toxic to neurons and leads to apoptosis.