title: Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background.
abstract: Retinol-binding protein 4 (RBP4) is a specific carrier for retinol in the blood. In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin and is secreted into the blood. The ternary transthyretin-RBP4-retinol complex transports retinol in the circulation and delivers it to target tissues. Rbp4-deficient mice in a mixed genetic background (129xC57BL/6J) have decreased sensitivity to light in the b-wave amplitude on electroretinogram. Sensitivity progressively improves and approaches that of wild-type mice at 24 weeks of age. In the present study, we produced Rbp4-deficient mice in the C57BL/6 genetic background. These mice displayed more severe phenotypes. They had decreased a- and b-wave amplitudes on electroretinograms. In accordance with these abnormalities, we found structural changes in these mice, such as loss of the peripheral choroid and photoreceptor layer in the peripheral retinas. In the central retinas, the distance between the inner limiting membrane and the outer plexiform layer was much shorter with fewer ganglion cells and fewer synapses in the inner plexiform layer. Furthermore, ocular developmental defects of retinal depigmentation, optic disc abnormality, and persistent hyaloid artery were also observed. All these abnormalities had not recovered even at 40 weeks of age. Our Rbp4-deficient mice accumulated retinol in the liver but it was undetectable in the serum, indicating an inverse relation between serum and liver retinol levels. Our results suggest that RBP4 is critical for the mobilization of retinol from hepatic storage pools, and that such mobilization is necessary for ocular development and visual function.
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Anesthesia, Daqing Oil field General Hospital, Daqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shi
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Center, Tsukuba, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Anesthesia, Fifth Hospital of Harbin, Harbin, China.
authors.forename: Zunping
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Anesthesia, Daqing Oil field General Hospital, Daqing, China.
authors.forename: Hanli
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.affiliation: Department of Anesthesia, Fifth Hospital of Harbin, Harbin, China.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.affiliation: Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Yamamura Project Laboratory, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamamura
authors.affiliation: Division of Respiratory Disease, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shoude
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.|Yamamura Project Laboratory, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D004596:Electroretinography; D005124:Eye Abnormalities / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D005654:Fundus Oculi; D055786:Gene Knockout Techniques / Q000379:methods; D008099:Liver / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000002:abnormalities; D054839:Retinol-Binding Proteins, Plasma / Q000172:deficiency* / Q000235:genetics; D014801:Vitamin A / Q000097:blood / Q000378:metabolism
chemical_list: C453730:Crb1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A