A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD.
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.
Fujihara
Masashi
M
Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Bartels
Emil
E
Nielsen
Lars B
LB
Handa
James T
JT
D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight; D002829:Choroid / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008268:Macular Degeneration / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D053299:Apolipoprotein B-100; D004041:Dietary Fats; D008055:Lipids; D012333:RNA, Messenger