Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice.

Authors: McLaughlin PJ; Bakall B; Choi J; Liu Z; Sasaki T; Davis EC; Marmorstein AD; Marmorstein LY

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.

Keywords: Aging, Premature/*genetics/pathology; Animals; Elastic Tissue/metabolism/pathology; Extracellular Matrix Proteins/*genetics/physiology; Fascia/metabolism/pathology; Hernia/*genetics/pathology; Longevity/genetics; Macular Degeneration/genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Reproduction/physiology; Wound Healing/physiology
Journal: Human molecular genetics
Volume: 16
Issue: 24
Pages: 3059-70
Date: Sept. 18, 2007
PMID: 17872905
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Citation:

McLaughlin PJ, Bakall B, Choi J, Liu Z, Sasaki T, Davis EC, Marmorstein AD, Marmorstein LY (2007) Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Human molecular genetics 16: 3059-70.


Study Lifespan Factors:
  • Efemp1 Epidermal growth factor-containing fibulin-like extracellular matrix protein 1


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