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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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. Maternal inheritance distinctive from imprinting and oocyte-derived mRNA mechanisms has been regarded as a rare exception unique to humans. Kaukonen et al. describe a canine model with a recessive maternally transmitted RBP4 defect, suggesting that this mechanism is more common in developmental defects.

Original languageEnglish (US)
Pages (from-to)2643-2652
Number of pages10
JournalCell Reports
Issue number9
StatePublished - May 29 2018


  • canine genetics
  • congenital eye defect
  • genome-wide association study
  • maternal inheritance
  • microphthalmia
  • nuclear magnetic resonance
  • RBP4
  • vitamin A
  • western blotting
  • whole genome sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease'. Together they form a unique fingerprint.

Cite this