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

Hum Mol Genet. 2007 Dec 15;16(24):3059-70. doi: 10.1093/hmg/ddm264. Epub 2007 Sep 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging, Premature / genetics*
  • Aging, Premature / pathology
  • Animals
  • Elastic Tissue / metabolism
  • Elastic Tissue / pathology
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / physiology
  • Fascia / metabolism
  • Fascia / pathology
  • Hernia / genetics*
  • Hernia / pathology
  • Longevity / genetics
  • Macular Degeneration / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Reproduction / physiology
  • Wound Healing / physiology


  • Efemp1 protein, mouse
  • Extracellular Matrix Proteins