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PMID:9353118

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Citation

Supp, DM, Witte, DP, Potter, SS and Brueckner, M (1997) Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389:963-6

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.

Links

PubMed PMC1800588 Online version:10.1038/40140

Keywords

Amino Acid Sequence; Animals; Axons/physiology; Body Patterning/genetics; Body Patterning/physiology; Chromosomes, Artificial, Yeast; Conserved Sequence; Dyneins/genetics; Dyneins/physiology; Embryo, Mammalian/metabolism; Gene Expression; Humans; Mice; Mice, Inbred Strains; Microtubule-Associated Proteins/genetics; Molecular Sequence Data; Mutation; Sequence Homology, Amino Acid; Situs Inversus/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:E9Q7N9

acts_upstream_of_or_within

GO:0007368: determination of left/right symmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856917

P

Seeded From UniProt

complete

MOUSE:H3BLD7

acts_upstream_of_or_within

GO:0007368: determination of left/right symmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856917

P

Seeded From UniProt

complete

MOUSE:Q9QZH1

acts_upstream_of_or_within

GO:0007368: determination of left/right symmetry

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856917

P

Seeded From UniProt

complete

See also

References

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