TY - JOUR
T1 - FE65 and FE65L1 amyloid precursor protein-binding protein compound null mice display adult-onset cataract and muscle weakness
AU - Suh, Jaehong
AU - Moncaster, Juliet A.
AU - Wang, Lirong
AU - Hafeez, Imran
AU - Herz, Joachim
AU - Tanzi, Rudolph E.
AU - Goldstein, Lee E.
AU - Guénette, Suzanne Y.
N1 - Publisher Copyright:
© FASEB.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - APP
KW - Congenital muscular dystrophy
KW - Extracellular matrix
KW - Laminin
KW - Lens
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U2 - 10.1096/fj.14-261453
DO - 10.1096/fj.14-261453
M3 - Article
C2 - 25757569
AN - SCOPUS:84933528791
SN - 0892-6638
VL - 29
SP - 2628
EP - 2639
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -