Increase of smooth muscle cell migration and of intimal hyperplasia in mice lacking the alpha/beta hydrolase domain containing 2 gene.
Multiple steps, including the migration of vascular smooth muscle cells (SMCs), are involved in the pathogenesis of atherosclerosis. To discover genes which are involved in these steps, we screened mutant mouse lines established by the exchangeable gene trap method utilizing X-gal staining during their embryonic development. One of these lines showed strong reporter gene expression in the vitelline vessels of yolk sacs at embryonic day (E) 12.5. The trap vector was inserted into the fifth intron of alpha/beta hydrolase domain containing 2 (Abhd2) gene which was shown to be expressed in vascular and non-vascular SMCs of adult mice. Although homozygous mutant mice were apparently normal, enhanced SMC migration in the explants SMCs culture and marked intimal hyperplasia after cuff placement were observed in homozygous mice in comparison with wild-type mice. Our results show that Abhd2 is involved in SMC migration and neointimal thickening on vascular SMCs.
Miyata
Keishi
K
Department of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, 4-24-1 Kuhonji, Kumamoto 862-0976, Japan.
Oike
Yuichi
Y
Hoshii
Takayuki
T
Maekawa
Hiromitsu
H
Ogawa
Hisao
H
Suda
Toshio
T
Araki
Kimi
K
Yamamura
Ken-ichi
K
D000818:Animals; D001011:Aorta / Q000473:pathology; D015152:Blotting, Northern; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005263:Femoral Artery / Q000473:pathology; D005697:Galactosides / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D005821:Genetic Techniques; D005838:Genotype; D022781:Hepatocytes / Q000378:metabolism; D006579:Heterozygote; D006867:Hydrolases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019076:Transgenes; D017539:Tunica Intima / Q000473:pathology*; D001616:beta-Galactosidase / Q000378:metabolism
D005697:Galactosides; D007211:Indoles; D012313:RNA; D006867:Hydrolases; C454240:Abhd2 protein, mouse; D001616:beta-Galactosidase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside