The Haploinsufficient Col3a1 Mouse as a Model for Vascular Ehlers-Danlos Syndrome
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Vascular Ehlers-Danlos syndrome is a rare genetic disorder resulting from mutations in the α-1 chain of type III collagen ( COL3A1) and manifesting as tissue fragility with spontaneous rupture of the bowel, gravid uterus, or large or medium arteries. The heterozygous Col3a1 knockout mouse was investigated as a model for this disease. The collagen content in the abdominal aorta of heterozygotes was reduced, and functional testing revealed diminishing wall strength of the aorta in these mice. Colons were grossly and histologically normal, but reduced strength and increased compliance of the wall were found in heterozygotes via pressure testing. Although mice demonstrated no life-threatening clinical signs or gross lesions of vascular subtype Ehlers-Danlos syndrome type IV, thorough histological examination of the aorta of heterozygous mice revealed the presence of a spectrum of lesions similar to those observed in human patients. Lesions increased in number and severity with age (0/5 [0%] in 2-month-old males vs 9/9 [100%] in 14-month-old males, P < .05) and were more common in male than female mice (23/26 [88.5%] vs 14/30 [46.7%] in 9- to 21-month-old animals, P < .05). Haploinsufficiency for Col3a1 in mice recapitulates features of vascular Ehlers-Danlos syndrome in humans and can be used as an experimental model.
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Two available mouse models for vEDS are homozygous or heterozygous nulls, which represent only about 5% or less of all known cases of vEDS patients.
“Currently, there are two available mouse models for vEDS, both are homozygous or heterozygous nulls, which represent only about 5% or less of all known cases of vEDS patients [13–15].”
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Felici, A., Angellotto, C., Ruta, A., Rongioletti, M. C. A., Versacci, P., & Mastromoro, G. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15145342
Shabaldin, N. A., Алексеевич, Р. Е., Кутихин, А. Г., Kenis, V. M., Sinitskaya, А. V., Stepanov, A. D., & Shabaldin, A. V. (2026) · Pediatric Traumatology Orthopaedics and Reconstructive Surgery · doi:10.17816/ptors705038
- Authors
- Cooper, T. K., Zhong, Q., Krawczyk, M., Tae, H.-J., Müller, G. A., Schubert, R., Myers, L. A., Dietz, H. C., Talan, M. I., & Briest, W.
- Affiliations
- Pennsylvania State University (US)
- National Institute on Aging (US)
- Heidelberg University (DE)
- Johns Hopkins University (US)
- Corresponding author
- Cooper, T. K.
- Venue
- Veterinary Pathology
- Publisher
- SAGE Publications
- Published
- 2010-06-29
- Volume
- 47
- Issue
- 6
- Pages
- 1028-1039
- ISSN
- 0300-9858 (ISSN-L)
- 1544-2217
- PMC
- PMC2970629
- OpenAlex
- W2148327933
- Cited by
- 51
- References
- 42
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Veterinary Pathology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute on Aging (ZIAAG000865)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041135)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Physical Sciences › Engineering › Biomedical Engineering › Elasticity and Material Modeling
- Keywords
- vascular Ehlers-Danlos syndrome, COL3A1, type III collagen, haploinsufficiency, aortic compliance, spontaneous arterial rupture, age-related disease progression, sex differences, disease models
- MeSH terms
- Animals, Aorta, Arteries, Blood Vessels, Colon, Disease Models, Animal, Ehlers-Danlos Syndrome, Female, Genotype, Heterozygote, Male, Blotting, Western, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Collagen Type III, Mice, Haploinsufficiency
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