Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease

Cell Reports
Maria KaukonenHannes Lohi

Abstract

Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. The maternal penetrance effect arises from an impairment in the sequential transfer of retinol across the placenta, via RBP encoded by maternal and fetal genomes. Our results demonstrate a mode of recessive maternal inheritance, with a physiological basis, and they extend previous observations on dominant-negative RBP4 alleles in humans.

Citations

Sep 6, 2019·Animal Genetics·V JagannathanUNKNOWN Dog Biomedical Variant Database Consortium (DBVDC)
May 9, 2019·Genesis : the Journal of Genetics and Development·Suya Wang, Alexander R Moise
Sep 26, 2020·Frontiers in Cellular Neuroscience·Jonathan EintrachtMariya Moosajee
Jan 25, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ioan Ovidiu SirbuAlexander Radu Moise
Oct 16, 2020·Veterinary Ophthalmology·Inês Q Saraiva, Esmeralda Delgado

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Methods Mentioned

BETA
electrophoresis
X-ray
immunoprecipitation
gel filtration
nuclear magnetic resonance
chemical shift
NMR

Software Mentioned

PLINK
GenABEL

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Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

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