Effects of retinoic acid on Dominant hemimelia expression in mice

Owen, MH; Ryan, LM; Holmes, LB

Effects of retinoic acid on Dominant hemimelia expression in mice

Owen, MH Ryan, LM

Holmes, LB

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Publication Type:: Journal Article
Citation:: Birth Defects Research Part A - Clinical and Molecular Teratology, 2009, 85 (1), pp. 36 - 41
Issue Date:: 2009-01-01

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Field	Value	Language
dc.contributor.author	Owen, MH	en_US
dc.contributor.author	Ryan, LM https://orcid.org/0000-0001-5957-2490	en_US
dc.contributor.author	Holmes, LB	en_US
dc.date.issued	2009-01-01	en_US
dc.identifier.citation	Birth Defects Research Part A - Clinical and Molecular Teratology, 2009, 85 (1), pp. 36 - 41	en_US
dc.identifier.issn	1542-0752	en_US
dc.identifier.uri	http://hdl.handle.net/10453/26124
dc.description.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. © 2008 Wiley-Liss, Inc.	en_US
dc.relation.ispartof	Birth Defects Research Part A - Clinical and Molecular Teratology	en_US
dc.relation.isbasedon	10.1002/bdra.20528	en_US
dc.subject.classification	Genetics & Heredity	en_US
dc.subject.mesh	Spine	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C3H	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Ectromelia	en_US
dc.subject.mesh	Abnormalities, Drug-Induced	en_US
dc.subject.mesh	Tretinoin	en_US
dc.subject.mesh	Homeodomain Proteins	en_US
dc.subject.mesh	Gene Expression Regulation, Developmental	en_US
dc.subject.mesh	Body Patterning	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Genes, Dominant	en_US
dc.subject.mesh	Genes, Homeobox	en_US
dc.subject.mesh	Female	en_US
dc.title	Effects of retinoic acid on Dominant hemimelia expression in mice	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	85	en_US
utslib.for	0104 Statistics	en_US
utslib.for	1114 Paediatrics and Reproductive Medicine	en_US
utslib.for	1117 Public Health and Health Services	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	85	en_US

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. © 2008 Wiley-Liss, Inc.

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http://hdl.handle.net/10453/26124