Marfan Syndrome Animal Model Development Services
Marfan syndrome is an autosomal dominant connective tissue disorder that affects the skeleton, eyes, and heart, and is systemic in nature. At Protheragen, we focus on the creation of high-quality mimetic models of human MFS for the purpose of advancing research in the field.
Overview of Marfan Syndrome Animal Models
Marfan Syndrome (MFS) is a complex genetic disorder characterized by abnormalities in the connective tissues, affecting various systems, including the skeleton, cardiovascular, and ocular systems. The primary genetic cause of MFS is mutations in the FBN1 gene, which encodes fibrillin-1, a key component of the extracellular matrix. These mutations lead to dysregulation of the transforming growth factor-beta (TGF-β) signaling pathway, resulting in the diverse phenotypic manifestations observed in MFS patients. Animal models play a crucial role in elucidating the pathophysiology of MFS and in the development of effective therapeutic strategies.
Fig.1 TGF-β pathway signaling in Marfan syndrome (MFS). (Maniati E., et al., 2020)
Types of Marfan Syndrome Animal Models
Animal models are crucial tools for studying MFS, and several types have been developed to mimic various aspects of the disease. Spontaneous models, such as the bovine model, naturally exhibit symptoms similar to human MFS, including lens dislocation and aortic pathology. Experimental models include genetically engineered mice, pigs, zebrafish, and rabbits, each created through targeted gene editing to replicate specific mutations found in human MFS. These models offer diverse advantages, from the detailed genetic manipulation capabilities of mice to the cardiovascular and ocular insights provided by rabbits and pigs. Each model type contributes uniquely to our understanding of MFS and the development of effective therapeutics.
Table 1. Advantages and disadvantages of animal models of MFS. (Maniati E., et al., 2020)
| Animal | Technical | Outcomes | Advantage | Disadvantage |
|---|---|---|---|---|
| Chicks | Drug feeding | Death by AA | Simple operation | No human genes given |
| Cattle | Multiply | AA, lordosis, elongated distal limbs, and lens ectasia | Can be passed on from one generation to the next | No human genes given |
| Mouse | Gene editing | fbn1mgΔ mouse | mgΔ/mgΔ mice showed cardiovascular abnormalities | A low extrinsic rate cannot produce offspring |
| mgR mouse | mgR/mgR Mouse similar to MFS. | A low extrinsic rate cannot produce offspring | ||
| C1039G mouse | C1039G/+ mouse is similar to MFS. | |||
| mgN mouse | mgN/mgN mice showed AA | Dead within 2 weeks | ||
| GT-8 mouse | Heterozygous mice showed AA | Homozygous mice die early after birth | ||
| H1Δ mouse | normal growth cycles | Without aortic lesions or microfiber defects | ||
| mgΔloxpneo mouse | Typical MFS phenotype | |||
| Pigs | Gene editing | Glu433AsnfsX98 | Similar to MFS | Long breeding cycle |
| Zebrafishes | Gene editing | fbn1+/-zebrafish | Similar to MFS | High fecundity and short life cycle |
| Caenorhabditis elegans | Gene editing | Mua-3 | MFS and MFS-like mutations in type II receptors | Little research |
| Rabbits | Gene editing | FBN1 Het rabbits | Typical features of MPL syndrome | Small sample size |
Our Services
Protheragen is at the forefront of Marfan Syndrome animal model development, offering high-quality, customized services to researchers worldwide. Our expertise in gene editing, phenotypic characterization, and therapeutic testing enables us to generate reliable and reproducible animal models that closely mimic human MFS.
Genetically Engineered Mouse Models (GEMMs)
| Model Types | Point Mutation Knockin Mice | Knockout Mice | Knockout Mice |
| Model Name | Fbn1-C1041G Mice | Fbn1-KO Mice | Mus81-KO Mice |
| Also Known As | C57BL/6-Fbn1em1(C1041G) | C57BL/6-Fbn1em | C57BL/6-Mus81em1 |
| Detailed Description | These mice carry a C1041G mutation of the Fbn1 gene. | Exon 65-66 of the Fbn1 gene was deleted to generate Fbn1 knockout mice. | Exons 1-10 of the Mus81 gene were deleted to generate Mus81 knockout mice. |
| NCBI ID | 14118 | 14118 | 71711 |
| MGI ID | 95489 | 95489 | 1918961 |
| Gene Alias | Tsk, Fib-1, AI536462, B430209H23 | Tsk, Fib-1, AI536462, B430209H23 | AI182501, AW045863, 1200008A18Rik |
| Chromosomes | Chr 2 | Chr 2 | - |
| Sales Status | Repository live | Embryo cryopreservation | Embryo cryopreservation |
| Applications & Therapeutic Areas | Marfan Syndrome | Marfan Syndrome | Research on homologous DNA pairing and strand exchange, and DNA double-strand break repair |
| Ensembl ID | ENSMUSG00000027204 | ENSMUSG00000027204 | ENSMUSG00000024906 |
| Pubmed | Fbn1 | Fbn1 | Mus81 |
| Human Ortholog | FBN1 | FBN1 | MUS81 |
Other Optional Species
Pig Models
Protheragen has also developed pig models of MFS using genome editing and somatic cell nuclear transplantation. These models exhibit phenotypes similar to human MFS, including scoliosis, funnel chest, and aortic anomalies.
Caenorhabditis Elegans Models
These models use the MUA-3 gene, which is homologous to fibrillin-1 in humans, to study MFS-related mutations and their effects on TGF-β signaling.
Zebrafish Models
Zebrafish models of MFS have been developed using CRISPR/Cas9 gene-editing technology. These models exhibit morphological and cardiovascular abnormalities similar to human MFS, making them a valuable tool for studying the molecular mechanisms underlying the disease.
Rabbit Models
Protheragen has developed rabbit models of MFS using CRISPR/Cas9 gene-editing technology. These models exhibit typical features of Marfan syndrome, including aortic dilatation and skeletal abnormalities. Rabbit models are particularly useful for studying the ocular and cardiovascular aspects of MFS.
Case Study
Fbn1C1041G/+ Mouse Model
At Protheragen, we specialize in developing advanced animal models for Marfan Syndrome (MFS) to support research and therapeutic development. Our Fbn1C1041G/+ mouse model accurately replicates key features observed in MFS patients, including aortic dilation, thoracic aortic aneurysms, aortic medial degeneration, and elastic lamina rupture. Additionally, we have observed reduced expression of PIEZO1 in these models, which aligns with findings in human MFS cases.
Fig 2. Reduced PIEZO1 expression in Marfan syndrome.
Protheragen offers flexible and customized services, from model generation to therapeutic testing, meeting the diverse needs of our clients. Our services are designed to accelerate the drug development process, reducing time and costs for our clients. If you are interested in our services, please feel free to contact us.
Reference
- Jiang, Yuanyuan, et al. "Marfan syndrome: insights from animal models." Frontiers in Genetics 15 (2025): 1463318.