Marfan Syndrome Animal Model Service

Marfan syndrome animal model service provides researchers with highly validated, genetically engineered models that faithfully recapitulate the human pathophysiology of Marfan syndrome, including aortic root dilation, elastic fiber fragmentation, and musculoskeletal manifestations. Protheragen offers comprehensive, custom-tailored in vivo studies, from initial model generation and phenotypic characterization to efficacy testing of novel therapeutic interventions, accelerating your drug discovery pipeline from target identification to robust preclinical proof-of-concept.

Introduction to Marfan Syndrome Animal Model

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. The resulting defect in microfibril formation leads to dysregulated TGF-β signaling, which drives the progression of the disease's cardinal features, most notably progressive aortic aneurysm and dissection. Animal models, particularly murine models, are indispensable for deciphering the complex pathogenesis of Marfan syndrome and for evaluating the efficacy and safety of potential therapeutics. These models serve as a critical bridge between in vitro findings and human trials, enabling the study of disease progression and drug effects in an organismal context.

Fig.1 Short-term rapamycin extends lifespan and delays aortic aneurysm in Marfan syndrome mice. (Katsandegwaza, B., et al., 2022)

Our Services

Leveraging our deep-seated expertise in cardiovascular diseases and translational research, we provide a comprehensive suite of services built on a foundation of animal models. Our team of scientists offers end-to-end support, encompassing custom model generation, detailed phenotypic monitoring, and rigorous efficacy testing of your candidate compounds, accelerating the progress of drug development and ensuring you receive reliable data to guide your research decisions.

Animal Models of Marfan Syndrome

Genetically Engineered Models

Protheragen provides comprehensive genetic engineering services to power your Marfan syndrome therapeutic discovery pipeline. We specialize in the precise development and validation of bespoke animal models, including the knock-in model and a range of knockout models. Utilizing advanced technologies, we deliver models that faithfully recapitulate the human disease pathophysiology, from progressive aortic root dilation to systemic connective tissue manifestations.

• Fbn1^C1041G/+
• Fbn1^mgΔ/mgΔ

• Fbn1^C1039G/+
• Others

Mouse Model for Marfan Syndrome Research

Case Study-FBN1^C1041G/+ Mouse Model Development

Model Introduction

Carrying a heterozygous point mutation (C1041G) in the Fbn1 gene on a C57BL/6 background, the FBN1^C1041G/+ mouse model serves as a well-characterized and genetically accurate model for Marfan syndrome, faithfully recapitulating the progressive aortic pathogenesis observed in individuals. Demonstrating a predictable timeline of disease progression, this model provides a robust platform for evaluating therapeutic interventions across various disease stages.

Methodology

• Animal Model: The established FBN1^C1041G/+ mouse model on a C57BL/6 background was utilized. To assess the effect of pathway modulation, a cohort of male Marfan syndrome mice received intraperitoneal administration of a receptor antagonist beginning at 3 months of age, every two days for one month. The age-matched control group received PBS injections.
• Phenotypic Analysis Methods
  • Aortic Echocardiography: Following hair removal and anesthesia, high-frequency ultrasound was used to image the aortic arch and abdominal aorta. Internal diameters of the aortic arch and abdominal aorta were measured from acquired images.
  • Morphometry Analysis of the Aorta: Ascending aortic samples were fixed, embedded, and cryosectioned. Aortic wall thickness was measured on H&E-stained sections, while elastic fiber integrity was evaluated via Verhoeff-Van Gieson (VVG) staining.

Phenotypic Analysis & Results

Consistent with the Marfan syndrome phenotype, significant elastin fragmentation was observed histologically in 3-month-old mutant mice, with pathology worsening by 6 months. Echocardiography revealed reduced diameters of the aortic arch and abdominal aorta in antagonist-treated Marfan syndrome mice compared with controls. Concurrently, elastic fiber staining showed decreased aortic wall thickness and fewer elastic fiber breaks in treated mice, indicating that the intervention attenuated aortic pathology in this Marfan syndrome model.

Fig.2 Pharmacological attenuation of aortic pathology in FBN1^C1041G/+ mice. Therapy with a pathway-targeting antagonist reduced aortic dilation and pathological remodeling, as shown by diameters of ascending (AsAo) and abdominal (AbAo) aortas (A-B), elastic fiber breaks (C), and medial thickness (D). Data are presented as mean ± SEM (n=5; **p < 0.01).

Conclusion

The data confirm that early pharmacological blockade of this pathway can successfully mitigate the development of aortic aneurysm and elastic fiber degeneration in a preclinical model. This work underscores the value of the FBN1^C1041G/+ model for validating novel therapeutic targets and provides compelling preclinical evidence to support the further investigation of targeted interventions for Marfan syndrome.

Contact Us

Protheragen's integrated solution is designed to take your project from concept to data. We go beyond basic animal models to offer a full spectrum of preclinical analyses, including detailed pharmacokinetics studies and drug safety and toxicology evaluations. We are your dedicated partner in advancing the therapeutic development of Marfan syndrome. Contact us today to discuss your specific project needs and how we can build a collaborative research plan to accelerate your therapeutic development.

Reference

• 1. Zaradzki, M et al. "Short-term rapamycin treatment increases life span and attenuates aortic aneurysm in a murine model of Marfan-Syndrome." Biochemical pharmacology 205 (2022): 115280.