Faculty Collaboration Database

Effects of retinoic acid on Dominant hemimelia expression in mice. Birth Defects Res A Clin Mol Teratol 2009 Jan;85(1):36-41

Date

12/17/2008

Pubmed ID

19086026

DOI

10.1002/bdra.20528

Scopus ID

2-s2.0-59849100128 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

BACKGROUND: Dominant hemimelia (Dh) is an autosomal dominant mutation that arose spontaneously in mice. Dh animals are asplenic and they exhibit asymmetric hindlimb defects in association with reduced numbers of lumbar vertebrae. These defects suggest that Dh acts early in embryonic development to affect patterning of the anterior-posterior (A-P) and left-right axes. This study was undertaken to determine whether retinoic acid (RA), which is involved in A-P patterning and coordination of bilaterally synchronized somitogenesis, affects phenotypic expression of the Dh gene.

METHODS: Thirty-four pregnant females were given, by oral intubation, a single dose of 50 or 75 mg all-trans RA per kilogram body weight at GD 9, 10, or 11. The pregnant females were then euthanized at GD 18 and fetuses removed by cesarean section. A total of 326 fetuses were identified by phenotype and linked DNA and their skeletons were analyzed.

RESULTS: There was a differential effect of RA on the axial skeleton and hindlimb of Dh/+ mice as compared to their wild-type littermates. Dose- and stage-specific effects on sternebrae and vertebrae were observed.

CONCLUSIONS: The effects of RA dosing on numbers of sternebrae and vertebrae suggest that Dh embryos have a primary defect in retinoid-mediated A-P patterning. Dosing with RA may produce the observed effects on phenotypic expression of Dh/+ by indirectly or directly modifying an already existing altered Hox expression pattern. As the relationship between axial patterning and the asymmetric limb is unknown, Dh is an important model for studying this relationship.

Author List

Owen MH, Ryan LM, Holmes LB

MESH terms used to index this publication - Major topics in bold

Abnormalities, Drug-Induced
Animals
Body Patterning
Dose-Response Relationship, Drug
Ectromelia
Female
Gene Expression Regulation, Developmental
Genes, Dominant
Genes, Homeobox
Homeodomain Proteins
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Pregnancy
Spine
Tretinoin