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

6533b833fe1ef96bd129c25c

RESEARCH PRODUCT

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

Saija Ahonen Seppo Lemberg Maria Kaukonen Maarit Hellman Perttu Permi Sean Woods Hannes Lohi Marjo K. Hytönen Thomas M Glaser

subject

0301 basic medicine Male Non-Mendelian inheritance Protein Folding congenital eye defect Eye Diseases genetic structures NATIVE DISULFIDE BONDS Medical Physiology Retinoic acid Reproductive health and childbirth 413 Veterinary science Microphthalmia vitamin A chemistry.chemical_compound Plasma A-vitamiini 2.1 Biological and endogenous factors Microphthalmos Prealbumin CRYSTAL-STRUCTURE Aetiology Base Pairing lcsh:QH301-705.5 Sequence Deletion Pediatric whole genome sequencing VITAMIN-A-DEFICIENCY ANOPHTHALMIA Penetrance Pedigree medicine.anatomical_structure Phenotype Female medicine.medical_specialty Genotype ENDOPLASMIC-RETICULUM Genes Recessive METABOLISM Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Dogs canine genetics Internal medicine Placenta RETINOL-BINDING-PROTEIN Genetics medicine Animals Humans Recessive MALFORMATIONS BIOCHEMICAL BASIS Amino Acid Sequence Allele Eye Disease and Disorders of Vision Nutrition genome-wide association study 030102 biochemistry & molecular biology western blotting MUTATIONS ta1184 RBP4 maternal inheritance medicine.disease Retinol-Binding Proteins Retinol binding protein nuclear magnetic resonance 030104 developmental biology Endocrinology chemistry Genes lcsh:Biology (General)microphthalmia Genetic Loci Hela Cells 1182 Biochemistry cell and molecular biology Congenital Structural Anomalies 3111 Biomedicine Biochemistry and Cell Biology Digestive Diseases Genomic imprinting Retinol-Binding Proteins Plasma HeLa Cells

description

SUMMARY 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.

year	journal	country	edition	language
2018-05-01

http://urn.fi/URN:NBN:fi:jyu-201805302923