Modeling Rare Bone Diseases in Animals

Abstract

Purpose of review: The goal of this review is to highlight some of the considerations involved in creating animal models to study rare bone diseases and then to compare and contrast approaches to creating such models, focusing on the advantages and novel opportunities offered by the CRISPR-Cas system.

Recent findings: Gene editing after creation of double-stranded breaks in chromosomal DNA is increasingly being used to modify animal genomes. Multiple tools can be used to create such breaks, with the newest ones being based on the bacterial adaptive immune system known as CRISPR/Cas. Advances in gene editing have increased the ease and speed, while reducing the cost, of creating novel animal models of disease. Gene editing has also expanded the number of animal species in which genetic modification can be performed. These changes have significantly increased the options for investigators seeking to model rare bone diseases in animals.

Keywords: Animal model; Gene-editing; Rare bone disease.

Figure 1. Gene Editing with CRISPR-Cas

The Cas9 nuclease (shown in yellow) is targeted to a specific sequence in the genome by a sgRNA. Such sequences must reside upstream from the sequence NGG. The double-strand DNA cut can be repaired by Non-Homologous End Joining (NHEJ) or by Homology Directed Repair (HDR). HDR requires donor DNA with homology to the regions flanking the cut site.