A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

Masashi Fujihara, Emil Bartels, Lars B. Nielsen, James Handa

Research output: Contribution to journalArticle

Abstract

apoB100 lipoprotein particles have been found to accumulate in Bruch membrane prior to the development of age-related macular degeneration (AMD). This work was performed to determine whether mice that overexpress apoB100 in the RPE/choroid and liver develop landmarks of early AMD over time. Mice transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated with early AMD were evaluated by ultrastructural analysis using transmission electron microscopy. Changes were semi-quantified using linear regression analysis. Both the RPE/choroid and liver of apoB100 mice expressed both human and mouse apoB mRNA. Transmission electron microscopy showed ultrastructural changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop validated phenotypic changes that are seen in early human AMD. The phenotypic changes were aggravated by feeding a high-fat diet. The apoB100 mouse model could be valuable in determining the role of apoB-containing lipoproteins in triggering the onset of early AMD.

Original languageEnglish (US)
Pages (from-to)1115-1123
Number of pages9
JournalExperimental Eye Research
Volume88
Issue number6
DOIs
StatePublished - Jun 1 2009

Fingerprint

Macular Degeneration
Transgenic Mice
Apolipoproteins B
High Fat Diet
Choroid
Bruch Membrane
Transmission Electron Microscopy
Lipoproteins
Liver
Linear Models
Regression Analysis
Messenger RNA
Vacuoles
Transgenes
Collagen
Genotype

Keywords

  • age-related macular degeneration
  • apolipoprotein B
  • basal laminar deposit
  • basal linear deposit
  • lipoproteins
  • retinal pigmented epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD. / Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B.; Handa, James.

In: Experimental Eye Research, Vol. 88, No. 6, 01.06.2009, p. 1115-1123.

Research output: Contribution to journalArticle

Fujihara, Masashi ; Bartels, Emil ; Nielsen, Lars B. ; Handa, James. / A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD. In: Experimental Eye Research. 2009 ; Vol. 88, No. 6. pp. 1115-1123.
@article{3e07822efda445b79c776ef2ebe2abbd,
title = "A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD",
abstract = "apoB100 lipoprotein particles have been found to accumulate in Bruch membrane prior to the development of age-related macular degeneration (AMD). This work was performed to determine whether mice that overexpress apoB100 in the RPE/choroid and liver develop landmarks of early AMD over time. Mice transgenic for a human genomic fragment encoding the full length human apoB ({"}apoB100{"} mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated with early AMD were evaluated by ultrastructural analysis using transmission electron microscopy. Changes were semi-quantified using linear regression analysis. Both the RPE/choroid and liver of apoB100 mice expressed both human and mouse apoB mRNA. Transmission electron microscopy showed ultrastructural changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop validated phenotypic changes that are seen in early human AMD. The phenotypic changes were aggravated by feeding a high-fat diet. The apoB100 mouse model could be valuable in determining the role of apoB-containing lipoproteins in triggering the onset of early AMD.",
keywords = "age-related macular degeneration, apolipoprotein B, basal laminar deposit, basal linear deposit, lipoproteins, retinal pigmented epithelium",
author = "Masashi Fujihara and Emil Bartels and Nielsen, {Lars B.} and James Handa",
year = "2009",
month = "6",
day = "1",
doi = "10.1016/j.exer.2009.01.017",
language = "English (US)",
volume = "88",
pages = "1115--1123",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",
number = "6",

}

TY - JOUR

T1 - A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

AU - Fujihara, Masashi

AU - Bartels, Emil

AU - Nielsen, Lars B.

AU - Handa, James

PY - 2009/6/1

Y1 - 2009/6/1

N2 - apoB100 lipoprotein particles have been found to accumulate in Bruch membrane prior to the development of age-related macular degeneration (AMD). This work was performed to determine whether mice that overexpress apoB100 in the RPE/choroid and liver develop landmarks of early AMD over time. Mice transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated with early AMD were evaluated by ultrastructural analysis using transmission electron microscopy. Changes were semi-quantified using linear regression analysis. Both the RPE/choroid and liver of apoB100 mice expressed both human and mouse apoB mRNA. Transmission electron microscopy showed ultrastructural changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop validated phenotypic changes that are seen in early human AMD. The phenotypic changes were aggravated by feeding a high-fat diet. The apoB100 mouse model could be valuable in determining the role of apoB-containing lipoproteins in triggering the onset of early AMD.

AB - apoB100 lipoprotein particles have been found to accumulate in Bruch membrane prior to the development of age-related macular degeneration (AMD). This work was performed to determine whether mice that overexpress apoB100 in the RPE/choroid and liver develop landmarks of early AMD over time. Mice transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated with early AMD were evaluated by ultrastructural analysis using transmission electron microscopy. Changes were semi-quantified using linear regression analysis. Both the RPE/choroid and liver of apoB100 mice expressed both human and mouse apoB mRNA. Transmission electron microscopy showed ultrastructural changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop validated phenotypic changes that are seen in early human AMD. The phenotypic changes were aggravated by feeding a high-fat diet. The apoB100 mouse model could be valuable in determining the role of apoB-containing lipoproteins in triggering the onset of early AMD.

KW - age-related macular degeneration

KW - apolipoprotein B

KW - basal laminar deposit

KW - basal linear deposit

KW - lipoproteins

KW - retinal pigmented epithelium

UR - http://www.scopus.com/inward/record.url?scp=67349093946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349093946&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2009.01.017

DO - 10.1016/j.exer.2009.01.017

M3 - Article

VL - 88

SP - 1115

EP - 1123

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

IS - 6

ER -