title: Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice.
abstract: A mutation in the EFEMP1 gene causes Malattia Leventinese, an inherited macular degenerative disease with strong similarities to age-related macular degeneration. EFEMP1 encodes fibulin-3, an extracellular matrix protein of unknown function. To investigate its biological role, the murine Efemp1 gene was inactivated through targeted disruption. Efemp1(-/-) mice exhibited reduced reproductivity, and displayed an early onset of aging-associated phenotypes including reduced lifespan, decreased body mass, lordokyphosis, reduced hair growth, and generalized fat, muscle and organ atrophy. However, these mice appeared to have normal wound healing ability. Efemp1(-/-) mice on a C57BL/6 genetic background developed multiple large hernias including inguinal hernias, pelvic prolapse and protrusions of the xiphoid process. In contrast, Efemp1(-/-) mice on a BALB/c background rarely had any forms of hernias, indicating the presence of modifiers for fibulin-3's function in different mouse strains. Histological analysis revealed a marked reduction of elastic fibers in fascia, a thin layer of connective tissue maintaining and protecting structures throughout the body. No apparent macular degeneration associated defects were found in Efemp1(-/-) mice, suggesting that loss of fibulin-3 function is not the mechanism by which the mutation in EFEMP1 causes macular degeneration. These data demonstrate that fibulin-3 plays an important role in maintaining the integrity of fascia connective tissues and regulates aging.
authors.affiliation: Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
authors.forename: Precious J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bakall
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: Alan D
authors.initials: AD
authors.lastname: Marmorstein
authors.forename: Lihua Y
authors.initials: LY
authors.lastname: Marmorstein
mesh_terms: D019588:Aging, Premature / Q000235:genetics* / Q000473:pathology; D000818:Animals; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000502:physiology; D005205:Fascia / Q000378:metabolism / Q000473:pathology; D006547:Hernia / Q000235:genetics* / Q000473:pathology; D008136:Longevity / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D012098:Reproduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: C492278:Efemp1 protein, mouse; D016326:Extracellular Matrix Proteins