Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease
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 an...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-05-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718307186 |
| _version_ | 1817995477304475648 |
|---|---|
| author | Maria Kaukonen Sean Woods Saija Ahonen Seppo Lemberg Maarit Hellman Marjo K. Hytönen Perttu Permi Tom Glaser Hannes Lohi |
| author_facet | Maria Kaukonen Sean Woods Saija Ahonen Seppo Lemberg Maarit Hellman Marjo K. Hytönen Perttu Permi Tom Glaser Hannes Lohi |
| author_sort | Maria Kaukonen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T02:07:43Z |
| format | Article |
| id | doaj.art-19030cb9d7154372b571c14092bec77c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-14T02:07:43Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-19030cb9d7154372b571c14092bec77c2022-12-22T02:18:37ZengElsevierCell Reports2211-12472018-05-012392643265210.1016/j.celrep.2018.04.118Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye DiseaseMaria Kaukonen0Sean Woods1Saija Ahonen2Seppo Lemberg3Maarit Hellman4Marjo K. Hytönen5Perttu Permi6Tom Glaser7Hannes Lohi8Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, FinlandDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, CA 95616, USADepartment of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, FinlandDepartment of Eye Diseases, Helsinki University Hospital, 00029 The Hospital District of Helsinki and Uusimaa, FinlandDepartment of Chemistry, Nanoscience Center, University of Jyväskylä, 40014 Jyväskylä, FinlandDepartment of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, FinlandDepartment of Chemistry, Nanoscience Center, University of Jyväskylä, 40014 Jyväskylä, FinlandDepartment of Cell Biology and Human Anatomy, University of California, Davis School of Medicine, Davis, CA 95616, USADepartment of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, FinlandMaternally 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.http://www.sciencedirect.com/science/article/pii/S2211124718307186microphthalmiaRBP4vitamin Acongenital eye defectwhole genome sequencinggenome-wide association studywestern blottingnuclear magnetic resonancecanine geneticsmaternal inheritance |
| spellingShingle | Maria Kaukonen Sean Woods Saija Ahonen Seppo Lemberg Maarit Hellman Marjo K. Hytönen Perttu Permi Tom Glaser Hannes Lohi Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease Cell Reports microphthalmia RBP4 vitamin A congenital eye defect whole genome sequencing genome-wide association study western blotting nuclear magnetic resonance canine genetics maternal inheritance |
| title | Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease |
| title_full | Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease |
| title_fullStr | Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease |
| title_full_unstemmed | Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease |
| title_short | Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease |
| title_sort | maternal inheritance of a recessive rbp4 defect in canine congenital eye disease |
| topic | microphthalmia RBP4 vitamin A congenital eye defect whole genome sequencing genome-wide association study western blotting nuclear magnetic resonance canine genetics maternal inheritance |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718307186 |
| work_keys_str_mv | AT mariakaukonen maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT seanwoods maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT saijaahonen maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT seppolemberg maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT maarithellman maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT marjokhytonen maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT perttupermi maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT tomglaser maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease AT hanneslohi maternalinheritanceofarecessiverbp4defectincaninecongenitaleyedisease |