The need for mouse models in osteoporosis genetics research

Abstract

Osteoporosis, the progressive loss of bone mass resulting in fragility fractures, affects ~ 75 million people in the United States, Europe and Japan. Bone mineral density (BMD) correlates with fracture risk and is widely used in clinical settings to predict fracture. Numerous studies have demonstrated that peak bone mass is highly heritable and consequently a number of genome-wide association studies (GWASs) have been conducted to identify the genes that regulate BMD. Traditional intercross mapping in the mouse has met with limited successes in the field of skeletal biology. With the advent of human GWAS, questions have arisen about the continued need for mouse models in genetics research. However, significant advances have been made in the field of mouse genetics, including new genetics resource populations and loci mapping techniques, which enable gene-level mapping resolution. In this review, we discuss the need for mouse models to help understand the skeletal biology underlying novel human GWAS findings, how loci discovered in the mouse can be used to complement GWAS analysis and highlight the recent advances made in the field of skeletal biology from the use of these new and developing resources. We conclude this paper with a discussion of the need for systems-level approaches in the skeletal biology field, with an emphasis on the need for pathway and network analyses.

The Progress of CRISPR/Cas9-Mediated Gene Editing in Generating Mouse/Zebrafish Models of Human Skeletal Diseases

“…The skeletal phenotypes of mice and humans are comparable both physiologically and anatomically. Micro-CT, digital X-ray microradiography and other techniques enable the characterization of the skeletal structure of mice [26,27]. An important advantage of the mouse model is the high homology between its genome and the human genome, which enables functional studies of human genes in this model [25].…”

Genetic regulation of bone strength: a review of animal model studies

“…At an average of 10 genes per Mb, 24 this equates to over 600 candidate genes, on average, per QTL. 25 As a result, the use of the two-strain, two-generation cross has started to fall out of favor for forward genetics studies. These two-strain populations are increasingly being replaced by studies using outbred populations of mice and rats.…”