Fibrous Dysplasia
The pathogenesis of fibrous dysplasia (FD) is still poorly understood, limiting the development of safe and effective therapies. In order to better understand this disease, our company is committed to developing multiple FD animal models with different strategies and characteristics. With our extensive experience and best-in-class technology, we provide our clients with comprehensive disease modeling services, including FD animal model generation and characterization, to support research in this field.
Background of Fibrous Dysplasia (FD)
FD is a rare genetic bone disease characterized by the abnormal growth of fibrous tissue instead of normal bone. It can affect a single bone (monostotic) or multiple bones (polyostotic) and may lead to skeletal deformities, fractures, and other complications. FD is caused by a mutation in the guanine nucleotide-binding protein gene (GNAS). This mutation can also lead to extraskeletal disease, which, when combined with FD, is called McCune-Albright syndrome (FD/MAS). Extraskeletal features usually involve the skin, endocrine tissue, and skeletal muscle. Due to the mosaic nature of the disease and the widespread expression of the stimulatory α-subunit of the guanine nucleotide-binding protein (Gαs), the presentation of FD/MAS is distinct. The diversity of phenotypic possibilities makes FD/MAS a complex and difficult disease to diagnose and manage.
Fig. 1 Fibrous dysplasia commonly affects the skull and is mosaic. (Lung H, et al., 2020)Our Services
We provide clients with several animal models to study FD pathogenesis, test potential therapeutic interventions, and evaluate the efficacy and safety of new drugs. We generate FD animal models using a variety of techniques, such as transgenic and gene editing approaches. Our services include, but are not limited to:
- We help our clients generate cell lines with GNAS point mutations and transgenic mice expressing GNAS point variants with osteoblast specificity. These transgenic mice develop skeletal damage very similar to human disease and can serve as useful FD models for pharmacological interventions.
- We develop FD mouse models of bone injury through activating mutations at the level of Gs-GPCR and transgenic expression or knockdown expression of GNAS alleles carrying R201C or R201H activating mutations. For example, we assist clients in developing a mouse model expressing GNAS-R201C in the bone stem cell lineage through a tetracycline-induced Cre-mediated Prrx1 driver.
Model Characteristics and Pharmacology Evaluation
We provide comprehensive analyses to fully characterize bone lesions and assess potential interventions. In addition, we can provide expertise in the design and execution of preclinical studies, including pharmacokinetic and pharmacodynamic studies, to evaluate the safety and efficacy of new drugs for FD. Our specific services include:
- Feature analysis (deformity, pain, fracture, and loss of vision, hearing, ambulation)
- Bone imaging analysis (appearance, density, and microarchitecture)
- Histology and histomorphometry analysis
- Histochemical and cellular marker analysis
- Blood and/or urine marker analysis (bone formation markers, bone resorption markers, and other markers)
Why Choose Us?
- Our team of scientists and technicians have extensive knowledge and expertise in the development and characterization of animal models of rare bone disorders, including FD.
- We have state-of-the-art facilities and equipment to support our disease modeling services, including advanced imaging technologies and molecular biology tools.
- We have a strong network of collaborators and partners in the academic and pharmaceutical sectors, who can help us stay up-to-date with the latest research trends and identify new opportunities for collaboration and innovation.
Our team of experts, state-of-the-art facilities, and commitment to quality and ethical standards make us a trusted partner for academic and pharmaceutical researchers seeking to advance the field of FD research. If you are interested in our disease modeling services, please contact us for more information.
Reference
- Lung, H.; et al. Advances in models of fibrous dysplasia/McCune-Albright syndrome. Frontiers in Endocrinology, 2020, 10: 925.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
