Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice.

@article{citeulike:3544893, abstract = {The development of characteristic visceral asymmetries along the left-right (LR) axis in an initially bilaterally symmetrical embryo is an essential feature of vertebrate patterning. The allelic mouse mutations inversus viscerum (iv) and legless (lgl) produce LR inversion, or situs inversus, in half of live-born homozygotes. This suggests that the iv gene product drives correct LR determination, and in its absence this process is randomized. These mutations provide tools for studying the development of LR-handed asymmetry and provide mouse models of human lateralization defects. At the molecular level, the normally LR asymmetric expression patterns of nodal and lefty are randomized in iv/iv embryos, suggesting that iv functions early in the genetic hierarchy of LR specification. Here we report the positional cloning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd), that is mutated in both lgl and iv. lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development. Our findings indicate that dynein, a microtubule-based motor, is involved in the determination of LR-handed asymmetry and provide insight into the early molecular mechanisms of this process.}, author = {Supp, D. M. and Witte, D. P. and Potter, S. S. and Brueckner, M.}, citeulike-article-id = {3544893}, doi = {10.1038/40140}, issn = {0028-0836}, journal = {Nature}, keywords = {lc4, thesis}, month = {October}, number = {6654}, pages = {963--966}, posted-at = {2008-11-16 21:33:30}, priority = {2}, title = {Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice.}, url = {http://dx.doi.org/10.1038/40140}, volume = {389}, year = {1997} }

TY - JOUR ID - citeulike:3544893 L3 - citeulike-article-id:3544893 N2 - The development of characteristic visceral asymmetries along the left-right (LR) axis in an initially bilaterally symmetrical embryo is an essential feature of vertebrate patterning. The allelic mouse mutations inversus viscerum (iv) and legless (lgl) produce LR inversion, or situs inversus, in half of live-born homozygotes. This suggests that the iv gene product drives correct LR determination, and in its absence this process is randomized. These mutations provide tools for studying the development of LR-handed asymmetry and provide mouse models of human lateralization defects. At the molecular level, the normally LR asymmetric expression patterns of nodal and lefty are randomized in iv/iv embryos, suggesting that iv functions early in the genetic hierarchy of LR specification. Here we report the positional cloning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd), that is mutated in both lgl and iv. lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development. Our findings indicate that dynein, a microtubule-based motor, is involved in the determination of LR-handed asymmetry and provide insight into the early molecular mechanisms of this process. IS - 6654 JF - Nature SN - 0028-0836 EP - 966 TI - Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. VL - 389 SP - 963 KW - lc4 KW - thesis AU - Supp, DM AU - Witte, DP AU - Potter, SS AU - Brueckner, M PY - 1997/10/30/ UR - http://dx.doi.org/10.1038/40140 ER -