Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome
Fibrillin is an evolutionarily ancient protein that lends elasticity and resiliency to a variety of tissues. In humans, mutations in fibrillin-1 cause Marfan and related syndromes, conditions in which the eye is often severely affected. To gain insights into the ocular sequelae of Marfan syndrome, w...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-01-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/12/1/dmm037283 |
| _version_ | 1818267828005896192 |
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| author | Wendell Jones Juan Rodriguez Steven Bassnett |
| author_facet | Wendell Jones Juan Rodriguez Steven Bassnett |
| author_sort | Wendell Jones |
| collection | DOAJ |
| description | Fibrillin is an evolutionarily ancient protein that lends elasticity and resiliency to a variety of tissues. In humans, mutations in fibrillin-1 cause Marfan and related syndromes, conditions in which the eye is often severely affected. To gain insights into the ocular sequelae of Marfan syndrome, we targeted Fbn1 in mouse lens or non-pigmented ciliary epithelium (NPCE). Conditional knockout of Fbn1 in NPCE, but not lens, profoundly affected the ciliary zonule, the system of fibrillin-rich fibers that centers the lens in the eye. The tensile strength of the fibrillin-depleted zonule was reduced substantially, due to a shift toward production of smaller caliber fibers. By 3 months, zonular fibers invariably ruptured and mice developed ectopia lentis, a hallmark of Marfan syndrome. At later stages, untethered lenses lost their polarity and developed cataracts, and the length and volume of mutant eyes increased. This model thus captures key aspects of Marfan-related syndromes, providing insights into the role of fibrillin-1 in eye development and disease. |
| first_indexed | 2024-12-12T20:28:47Z |
| format | Article |
| id | doaj.art-5da8c414ac02403ca0a7b8c73a136cca |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-12T20:28:47Z |
| publishDate | 2019-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-5da8c414ac02403ca0a7b8c73a136cca2022-12-22T00:13:04ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-01-0112110.1242/dmm.037283037283Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndromeWendell Jones0Juan Rodriguez1Steven Bassnett2 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave, Box 8096, St. Louis, MO 63117, USA St Louis College of Pharmacy, Department of Basic Sciences, 4588 Parkview Place, St. Louis, MO 63110, USA Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave, Box 8096, St. Louis, MO 63117, USA Fibrillin is an evolutionarily ancient protein that lends elasticity and resiliency to a variety of tissues. In humans, mutations in fibrillin-1 cause Marfan and related syndromes, conditions in which the eye is often severely affected. To gain insights into the ocular sequelae of Marfan syndrome, we targeted Fbn1 in mouse lens or non-pigmented ciliary epithelium (NPCE). Conditional knockout of Fbn1 in NPCE, but not lens, profoundly affected the ciliary zonule, the system of fibrillin-rich fibers that centers the lens in the eye. The tensile strength of the fibrillin-depleted zonule was reduced substantially, due to a shift toward production of smaller caliber fibers. By 3 months, zonular fibers invariably ruptured and mice developed ectopia lentis, a hallmark of Marfan syndrome. At later stages, untethered lenses lost their polarity and developed cataracts, and the length and volume of mutant eyes increased. This model thus captures key aspects of Marfan-related syndromes, providing insights into the role of fibrillin-1 in eye development and disease.http://dmm.biologists.org/content/12/1/dmm037283Marfan syndromeCiliary zonuleEctopia lentisFibrillin-1Non-pigmented ciliary epitheliumLens |
| spellingShingle | Wendell Jones Juan Rodriguez Steven Bassnett Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome Disease Models & Mechanisms Marfan syndrome Ciliary zonule Ectopia lentis Fibrillin-1 Non-pigmented ciliary epithelium Lens |
| title | Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome |
| title_full | Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome |
| title_fullStr | Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome |
| title_full_unstemmed | Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome |
| title_short | Targeted deletion of fibrillin-1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with Marfan syndrome |
| title_sort | targeted deletion of fibrillin 1 in the mouse eye results in ectopia lentis and other ocular phenotypes associated with marfan syndrome |
| topic | Marfan syndrome Ciliary zonule Ectopia lentis Fibrillin-1 Non-pigmented ciliary epithelium Lens |
| url | http://dmm.biologists.org/content/12/1/dmm037283 |
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