遺伝子改変動物を利用した形態形成機構の解明(病理領域における新しい解析方法の導入)

概要

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Though left and right of our body have symmetrical outlook, almost all inside organs are asymmetrically arranged such that the dextral looping of the heart in vertebrate development, variations in the number of lung lobes on the two sides in mammals and the direction of the gut rotation. Determination of right and left has been proved to be genetically controlled. Genetic mutants which affect the left-right asymmetry have a tremendous value to elucidate the left-right formation. Advancement of molecular biology and embryo handling have made it possible to produce genetically engineered animals. By random mutagenesis using microinjection of the tyrosinase minigene into mouse one cell stage embryos, we created a new situs inversus (inv) mutation. The inv homozygous mice for the transgene (inv/inv) showed nearly 100% reversal of left-right polarity. Previously reported iv/iv mutant reverses left-right polarity approximately 50%. No more than 50% of experimentally manipulated amphibian and mouse embryos produces situs inversus phenotype. Based on consistent reversal of left-right asymmetry in our new situs inversus mutation, we proposed the possible existence of a default or pre-existent pathway for left-right asymmetry. The inv locus has been found on mouse chromosome 4, determined by linkage analysis and FISH (fluorescein in situ hybridization) study. The approach to isolate the gene was discussed.
東京女子医科大学の論文
1996-05-25