FE65 and FE65L1 amyloid precursor protein-binding protein compound null mice display adult-onset cataract and muscle weakness

Jaehong Suh, Juliet A. Moncaster, Lirong Wang, Imran Hafeez, Joachim Herz, Rudolph E. Tanzi, Lee E. Goldstein, Suzanne Y. Guénette

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

FE65 and FE65L1 are cytoplasmic adaptor proteins that bind a variety of proteins, including the amyloid precursor protein, and that mediate the assembly of multimolecular complexes. We previously reported that FE65/FE65L1 double knockout (DKO) mice display disorganized laminin in meningeal fibroblasts and a cobblestone lissencephaly-like phenotype in the developing cortex. Here, we examined whether loss of FE65 and FE65L1 causes ocular and muscular deficits, 2 phenotypes that frequently accompany cobblestone lissencephaly. Eyes of FE65/FE65L1 DKO mice develop normally, but lens degeneration becomes apparent in young adultmice. Abnormal lens epithelial cell migration, widespread small vacuole formation, and increased laminin expression underneath lens capsules suggest impaired interaction between epithelial cells and capsular extracellular matrix in DKO lenses. Cortical cataracts develop in FE65L1 knockout (KO) mice aged 16 months or more but are absent inwild-type or FE65KOmice.FE65 familyKOmice show attenuated grip strength, and the nuclei of DKO muscle cells frequently locate in the middle of muscle fibers. These findings reveal that FE65 and FE65L1 are essential for the maintenance of lens transparency, and their loss produce phenotypes in brain, eye, and muscle that are comparable to the clinical features of congenital muscular dystrophies in humans.

Original languageEnglish (US)
Pages (from-to)2628-2639
Number of pages12
JournalFASEB Journal
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • APP
  • Congenital muscular dystrophy
  • Extracellular matrix
  • Laminin
  • Lens

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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    Suh, J., Moncaster, J. A., Wang, L., Hafeez, I., Herz, J., Tanzi, R. E., Goldstein, L. E., & Guénette, S. Y. (2015). FE65 and FE65L1 amyloid precursor protein-binding protein compound null mice display adult-onset cataract and muscle weakness. FASEB Journal, 29(6), 2628-2639. https://doi.org/10.1096/fj.14-261453