Osteogenesis imperfecta (OI) is an inheritable skeletal disorder characterized by bone fragility often caused by pathogenic variants in the COL1A1 gene. Current OI mouse models with a glycine substitution in Col1a1 exhibit excessive severity, thereby limiting long-term pathophysiological analysis and drug effect assessments. To address this limitation, we constructed a novel OI mouse model mimicking a patient with OI type III. This was achieved by introducing a G-to-A transversion at nucleotide position 2428 in the Col1a1 gene via CRISPR-Cas9 technology in C57BL/6 J mice. The resulting heterozygous variant mice (Col1a1) displayed reduced body weight and pronounced skeletal abnormalities. Micro-CT analysis at 12 weeks revealed decreased vertebral bone parameters and altered cortical bone characteristics, indicative of bone fragility. Additionally, the abnormalities of the anisotropy, complexity, connectivity, and structure of trabecular bone were revealed. A three-point bending test confirmed the fragility, with reduced displacement and fracture energy in both sexes. Furthermore, we evaluated the effect of 4-phenylbutyric acid on the bone in Col1a1 mice at 12 weeks, observing no significant effects, likely due to the absence of collagen retention in the ER in this model. Despite being a moderate OI model, Col1a1 mice manifest a distinct and fragile bone phenotype, making them suitable for extended studies. This model offers a valuable platform for investigating long-term pathophysiological aspects of OI and assessing the efficacy of potential therapeutic interventions.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-024-01320-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698804PMC

Publication Analysis

Top Keywords

osteogenesis imperfecta
8
mouse model
8
bone fragility
8
col1a1 gene
8
long-term pathophysiological
8
col1a1 mice
8
col1a1
7
bone
7
model
5
characterization novel
4

Similar Publications

Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI.

View Article and Find Full Text PDF

Osteogenesis imperfecta (OI) is an inheritable skeletal disorder characterized by bone fragility often caused by pathogenic variants in the COL1A1 gene. Current OI mouse models with a glycine substitution in Col1a1 exhibit excessive severity, thereby limiting long-term pathophysiological analysis and drug effect assessments. To address this limitation, we constructed a novel OI mouse model mimicking a patient with OI type III.

View Article and Find Full Text PDF

Osteogenesis imperfecta (OI) is a fairly common generalized connective disorder characterized by low bone mass, bone deformities and impaired bone quality that predisposes affected individuals to musculoskeletal fragility. Periodontal ligament (PDL)-alveolar bone and PDL-cementum entheses' roles under OI conditions during physiological loading and orthodontic forces remain largely unknown. In addition, bisphosphonates (e.

View Article and Find Full Text PDF

A symbiotic relationship exists between narrative imaginaries of and real-life advancements in technology. Such cultural imaginings have a powerful influence on our understanding of the potential that technology has to affect our lives; as a result, narrative-based approaches to (PD) of technology are an active area of investigation.In this ongoing study, the following research questions are addressed: how can PD be optimised for the fields of robotics and assistive technology, particularly with regard to fostering empowerment and eliciting how people imagine the role of technology in their own futures? How can the symbiotic relationship between (popular) cultural imaginaries and real-life technological advancements be acknowledged within the PD process?The study synthesises fictional inquiry and science fiction prototyping methodologies and processes over multiple workshops.

View Article and Find Full Text PDF

Purpose: Osteogenesis imperfecta (OI) is a rare hereditary disorder of the connective tissue. Despite recent attention to corneal abnormalities in OI, understanding remains limited. This study aimed to comprehensively evaluate corneal changes in a large sample of OI patients compared to controls using in vivo confocal microscopy (IVCM).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!