Selection of experimental animals and modeling methods in developmental dysplasia of the hip research

Abstract

Developmental dysplasia of the hip (DDH) is a common neonatal musculoskeletal condition characterized by hip instability and inadequate acetabular coverage. If untreated, it can lead to osteoarthritis, chronic pain, and eventual hip replacement. Animal models, including dogs, pigs, sheep, rabbits, rodents, and chickens, are essential tools for studying DDH pathogenesis and testing therapeutic strategies. Larger species closely resemble human anatomy, while smaller species facilitate cost-effective, high-throughput studies and advanced genetic manipulation. Key modeling strategies include surgical interventions (e.g. joint dislocation, femoral or pelvic osteotomy), external fixation, and genetic modifications (e.g. gene knockout or lentiviral transduction) to simulate various aspects of DDH and reflect its multifactorial etiology. Evaluation techniques such as radiography, microcomputed tomography, MRI, and ultrasound are employed to image bony and cartilaginous structures. Histological and immunohistochemical analyses provide insights into cellular and extracellular matrix changes, while gait assessments evaluate functional deficits and pain-related behaviors. Selecting an appropriate animal model requires careful consideration of research objectives, ethical standards, and translational potential. Advances in gene editing technologies (e.g. CRISPR), three-dimensional-printed implants, and in vivo imaging are enhancing model fidelity and accelerating the discovery of novel therapies. Ongoing innovations in DDH research are expected to bridge gaps in understanding the disease's etiology and improve long-term outcomes for affected patients through optimized therapeutic interventions.

Keywords: animal models; developmental dysplasia of the hip; evaluation protocols; genetic manipulation; transgenic animals.

Figure 1

General workflow for generating and validating transgenic mouse models in DDH. Created in https://BioRender.com). The generation of genetically modified mouse models for DDH involves four key steps: (1) identification of candidate pathogenic mutations through pedigree analysis, sequencing of large sporadic populations, or genetic data mining; (2) validation of identified variants in sporadic DDH patient samples; (3) creation of knock-in or knockout mouse models via CRISPR/Cas9 gene editing; and (4) functional validation of mutations and assessment of their impacts on acetabular development using imaging and histopathological analyses.

Figure 2

The schematic diagram of common animal models for developmental hip dysplasia (created in https://BioRender.com).

Figure 3

Decision tree for choosing appropriate animal models in DDH studies. This schematic uses different colors to distinguish between research objectives such as investigating disease etiology, risk factors, natural history, and treatment development. For each objective, lines of the same color connect the applicable animal species and modeling approaches, indicating suitable combinations. When a single modeling method connects to multiple objectives, it suggests cross-applicability across different research goals.