Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genetics. 2005 May;170(1):345-53. Epub 2005 Mar 21.

A gene(s) for all-trans-retinoic acid-induced forelimb defects mapped and confirmed to murine chromosome 11.

Author information

  • 1Molecular Toxicology Interdepartmental Program, UCLA School of Public Health, Los Angeles, California 90095, USA.

Abstract

All-trans-retinoic acid (RA) induces various anatomical limb dysmorphologies in mice dependent on the time of exposure. During early limb development, RA induces forelimb ectrodactyly (digital absence) with varying susceptibilities for different inbred mouse strains; C57BL/6N are highly susceptible while SWV are resistant. To isolate the genetic basis of this defect, a full-genome scan was performed in 406 backcross fetuses of F(1) males to C57BL/6N females. Fetuses were exposed via a maternal injection of 75 mg of RA per kilogram of body weight on gestational day 9.25. The genome-wide analysis revealed significant linkage to a chromosome 11 locus near D11Mit39 with a maximum LOD score of 9.0 and to a chromosome 4 locus near D4Mit170. An epistatic interaction was detected between loci on chromosome 11 (D11Mit39) and chromosome 18 (D18Mit64). Linkage to the chromosome 11 locus (D11Mit39) was confirmed in RA-treated backcross fetuses of F(1) females to C57BL/6N males. Loci associated with bone density/mass in both human and mouse were previously detected in the same region, suggesting a mechanistic linkage with bone homeostasis. The human syntenic region of this locus has been previously linked to Meckel syndrome; the phenotype includes postaxial polydactyly, an ectopic digital defect hypothesized to be induced by a common molecular pathway with ectrodactyly.

PMID:
15781699
[PubMed - indexed for MEDLINE]
PMCID:
PMC1449723
Free PMC Article

Images from this publication.See all images (4)Free text

F igure  1.—
F igure  2.—
F igure  3.—
F igure  4.—
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk