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Interaction of Genotype and Dietary Vitamin A in Cleft Lip and/or Palate

唇裂和/或腭裂基因型与膳食维生素 A 的相互作用

基本信息

批准号：
8979370
负责人：
Sara M Rolfe
金额：
$ 5.32万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-08 至 2018-09-07
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8979370
关键词：
Address Age Alleles Animals Bioavailable Breathing Cleaved cell Cleft Lip Clinical Collaborations Complex Congenital Abnormality Custom Data Set Development Diet Disease Embryo Embryonic Development Environmental Risk Factor Face Frequencies Future Genetic Genetic Predisposition to Disease Genotype Goals Heterogeneity Human Hybrids Image Intervention Knock-out Knockout Mice Lead Lip structure Measures Methods Modeling Morphology Mouse Strains Palate Partner in relationship Pathway interactions Pattern Penetrance Phenotype Predisposition Prevention strategy Resolution Retinoids Retinol Binding Proteins Role Serum Severities Speech Development Staging Structure Supplementation Universities Vitamin A Vitamin A Deficiency Wit Work cleft lip and palate clinical effect craniofacial development dietary control embryo tissue feeding interest male mother nutrition mouse model mutant nutrition postnatal professor protective effect public health relevance tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Clefting of the lip and/or palate (CL/P) is the most common facial birth defect. This disruption of normal facial structure can lead to difficulties wit necessary functions such as breathing, feeding, and speech development. Clinical manifestations of CL/P are highly variable, indicating that the disorder is likely caused by a complex interaction of genetic and environmental factors. There is currently great interest in identifying the environmental factors that interact with genetic susceptibility to effect clinical presentation of CL/P, as further understanding of these factors could lead to important new treatments and interventions. Maternal nutrition is both a known influence on craniofacial development and an ideal target for future interventions. This project will investigate how genotype and vitamin A levels in the maternal diet interact to influence midfacial development and CL/P susceptibility and severity. In the first aim of this project, a mouse model allowing precise control over bioavailable levels of vitamin A will be used to assess the impact of mild and moderate maternal vitamin A deficiency (VAD) on facial phenotype. Using deformable morphology analysis, difference in phenotypes will be quantified and are expected to reveal a graded degree of change in facial morphology corresponding to the degree of maternal VAD. The second aim of this project will use mouse models allowing dietary control of vitamin A and/or CL/P sensitivity to investigate the impact of mild and moderate maternal VAD and maternal vitamin A supplementation on CL/P severity and frequency. Severity of phenotypes will be quantified using deformable morphology methods. The results are expected to show an increase in cleft severity and frequency corresponding to the degree of maternal VAD and a protective effect associated with vitamin A supplementation. This work will further the understanding of the underlying mechanisms and environmental modulators contributing to CL/P susceptibility and sensitivity which will help identify optimal treatment and preventative strategies.