Mouse Models in Tendon and Ligament Research

Abstract

Mutant mouse models are valuable resources for the study of tendon and ligament biology. Many mutant mouse models are used because their manifested phenotypes mimic clinical pathobiology for several heritable disorders, such as Ehlers-Danlos Syndrome and Osteogenesis Imperfecta. Moreover, these models are helpful for discerning roles of specific genes in the development, maturation, and repair of musculoskeletal tissues. There are several categories of genes with essential roles in the synthesis and maintenance of tendon and ligament structures. The form and function of these tissues depend highly upon fibril-forming collagens, the primary extracellular macromolecules of tendons and ligaments. Models for these fibril-forming collagens, as well as for regulatory molecules like FACITs and SLRPs, are important for studying fibril assembly, growth, and maturation. Additionally, mouse models for growth factors and transcription factors are useful for defining regulation of cell proliferation, cell differentiation, and cues that stimulate matrix synthesis. Models for membrane-bound proteins assess the roles of cell-cell communication and cell-matrix interaction. In some cases, special considerations need to be given to spatio-temporal control of a gene in a model. Thus, conditional and inducible mouse models allow for specific regulation of genes of interest. Advances in mouse models have provided valuable tools for gaining insight into the form and function of tendons and ligaments.

Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci

“…38 We speculate that LUM might regulate the downstream collagen genes that are important for CAD development. This notion is supported by the literature evidence on the role of LUM in collagen fibrillogenesis in CAD 39,40 and the enrichment of collagen genes such as COL3A1 and COL8A1 in the LUM subnetworks found in our analysis. Interestingly, the LUM subnetworks are also enriched for genes important for complement and coagulation cascades, such as SERPING1 , CFH , and TFPI , which have been implicated in CAD development.…”

Regulation of corneal stroma extracellular matrix assembly

“…Mouse models have demonstrated that SLRPs are critical regulators of collagen fibrillogenesis, particularly the linear and lateral growth of protofibrils into mature fibrils (Chakravarti et al, 1998; Chakravarti et al, 2003; Chakravarti et al, 2006; Chen and Birk, 2013; Chen et al, 2010; Ezura et al, 2000; Mienaltowski and Birk, 2014a; Zhang et al, 2009). Mice that are deficient in decorin or biglycan only have a mild corneal phenotype.…”

Transcriptome profiles of isolated murine Achilles tendon proper‐ and peritenon‐derived progenitor cells

“…For fifteen individual TP progenitor colonies and fifteen individual PERI colonies with diameters greater than or equal to 5 mm, expression levels were quantified by real‐time quantitative polymerase chain reaction assay (RT‐qPCR) for target genes Adamts16 , Fgl2 , Fmod , Gdf5 , Itga4 , Mkx , Scx , Thbs4 , and Wnt10a , as well as housekeeping gene Polr2a (Table ) . These genes were selected because their expression had been previously determined to be associated with certain cell types like tendon cells, pericytes, and vascular endothelium . Polr2a was determined to be the most stable gene for gene expression normalization via two strategies (Supplemental Data 1: Fig.…”

“…2,6,20,21 These genes were selected because their expression had been previously determined to be associated with certain cell types like tendon cells, pericytes, and vascular endothelium. [22][23][24][25][26][27][28][29][30][31][32][33][34] Polr2a was determined to be the most stable gene for gene expression normalization via two strategies (Supplemental Data 1: Fig. S-1 and Tables S-1-S-3).…”