Abnormal development of the Retina and Reduced Bone Mass in Rats Deficient in in Lrp5: A Human Disease Model Developed Using CRISPR/Cas9

Guest Speaker: John Ubels, Calvin University (Emeriti- Biology Department)

The Wnt signaling pathway controls normal development of bone and retina. Loss of function mutations of the Wnt co-receptor, Lrp5, result in decreased bone mass and density and impaired development of the retinal blood vessels. In children, this can result in osteoporosis by the age of 5 and blindness. Using CRISPR/Cas9, we have developed a rat model of this disease in which bone pathology is very similar to humans. The retinal blood vessels are sparce and leaky, the retina is thin and the response to light is impaired. This rat model will be useful for understanding human Lrp5 mutations and the development of treatment that can restore Lrp5 function.