| Autor: |
Ubels JL; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA.; Department of Biology, Calvin University, Grand Rapids, Michigan, USA., Diegel CR; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA., Foxa GE; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA., Ethen NJ; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA., Lensing JN; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA., Madaj ZB; Core Technologies and Services, Van Andel Institute, Grand Rapids, Michigan, USA; Calvin University, Grand Rapids, Michigan, USA., Williams BO; Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, and Calvin University, Grand Rapids, Michigan, USA. |
| Abstrakt: |
Humans carrying homozygous loss-of-function mutations in the Wnt co-receptor, low-density lipoprotein receptor-related protein 5 (LRP5), develop osteoporosis and a defective retinal vasculature known as familial exudative vitreoretinopathy (FEVR) due to disruption of the Wnt signaling pathway. The purpose of this study was to use CRISPR-Cas9-mediated gene editing to create strains of Lrp5-deficient rats and to determine whether knockout of Lrp5 resulted in phenotypes that model the bone and retina pathology in LRP5-deficient humans. Knockout of Lrp 5 in rats produced low bone mass, decreased bone mineral density, and decreased bone size. The superficial retinal vasculature of Lrp5-deficient rats was sparse and disorganized, with extensive exudates and decreases in vascularized area, vessel length, and branch point density. This study showed that Lrp 5 could be predictably knocked out in rats using CRISPR-Cas9, causing the expression of bone and retinal phenotypes that will be useful for studying the role of Wnt signaling in bone and retina development and for research on the treatment of osteoporosis and FEVR. |
