A mouse model of brittle cornea syndrome type 2

Abstract

AbstractPurpose: Brittle Cornea Syndrome (BCS) is a rare disease that affects 1 in 1 000 000 people world wide. With a reduction in cornea thickness and therefore strength sufferers have an increase in loss of vision through injury. Our lab has previously published the first mouse model of BCS Type 1(1) and are currently characterizing a novel model of BCS type 2 in order to elucidate the underlying mechanisms causing this disease.Methods: Mice carrying a 7 bp deletion which causes a frameshift and premature stop codon within the causative gene Prdm5 have been extensively phenotyped using Optical Coherence Tomography (OCT), Transmission Electron Microscopy (TEM) and Histology.Results: These mice show a reduced central corneal thickness by OCT from as early as 1 month of age. TEM and histological analysis indicates that this reduction in thickness may be due to the dysregulation of collagen assembly – as stromal collagen fibre diameter is significantly reduced.Conclusions: The structure of the stroma is crucial to corneal function: mechanical strength and transparency are achieved by the intricate arrangement of collagen fibrils, synthesized by keratocytes. Although it is known that the corneal stroma has a unique composition in which the ratio of Type I to Type V collagen is very different to anywhere else in the body, it remains unclear how the synthesis and maintenance of this specialized extracellular matrix by keratocytes is controlled. Characterization of the nature and extent of developmental defects in the cornea of this mouse model will be important to devise future therapeutic interventions.Reference1. Stanton, C. M., Findlay, A. S., Drake, C., Mustafa, M. Z., Gautier, P., McKie, L., Jackson, I. J., & Vitart, V. (2021). A mouse model of brittle cornea syndrome caused by mutation in Zfp469. Disease models & mechanisms, 14(9), dmm049175. https://doi.org/10.1242/dmm.049175