Maternal nutrition determines the variable expressivity of STRA6-associated eye malformations
Aicha Saadane1, Johannes von Lintig1
1Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Summary
Maternal vitamin A levels significantly impact Matthew-Wood syndrome outcomes in mice. Proper vitamin A intake is crucial for normal ocular development and survival in STRA6-related disorders.
Area of Science:
- Genetics and Developmental Biology
- Nutritional Science
- Ophthalmology
Background:
- Matthew-Wood syndrome, caused by STRA6 mutations, exhibits variable expressivity and incomplete penetrance.
- The underlying mechanisms for this variability, particularly concerning ocular development, are not well understood.
- STRA6 is the high-affinity receptor for retinol-binding protein, crucial for vitamin A transport.
Purpose of the Study:
- To investigate the interaction between maternal vitamin A status and embryonic Stra6 genotype in shaping ocular development.
- To elucidate the mechanisms behind the variable expressivity and incomplete penetrance of STRA6-associated disorders.
Main Methods:
- Utilized Stra6-deficient (Stra6-/-) and heterozygous (Stra6+/-) mouse models.
- Manipulated maternal vitamin A intake (restriction, sufficient, supraphysiological).
- Assessed ocular development, postnatal survival, and retinoid availability in offspring.
Main Results:
- Maternal vitamin A restriction led to microphthalmia and reduced survival in Stra6-/- offspring.
- Even with sufficient vitamin A, Stra6-/- offspring exhibited ocular abnormalities like retinal dysplasia.
- Supraphysiological maternal vitamin A partially rescued ocular development.
- Stra6+/- offspring from Stra6-/- dams were protected from lethality and ocular defects.
Conclusions:
- Maternal vitamin A status is a critical modifier of phenotypic outcome in STRA6-associated disease.
- Ocular retinoid availability is dependent on offspring's Stra6 genotype.
- Gene-nutrient interactions, specifically between STRA6 and vitamin A, explain disease variability and incomplete penetrance.
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