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A crystallin mutant cataract with mineral deposits.
Minogue, Peter J; Gao, Junyuan; Mathias, Richard T; Williams, James C; Bledsoe, Sharon B; Sommer, Andre J; Beyer, Eric C; Berthoud, Viviana M.
Afiliação
  • Minogue PJ; Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.
  • Gao J; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA.
  • Mathias RT; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, USA.
  • Williams JC; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Bledsoe SB; Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Sommer AJ; Molecular Microspectroscopy Laboratory, Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA.
  • Beyer EC; Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.
  • Berthoud VM; Department of Pediatrics, University of Chicago, Chicago, Illinois, USA. Electronic address: vberthou@bsd.uchicago.edu.
J Biol Chem ; 299(8): 104935, 2023 08.
Article em En | MEDLINE | ID: mdl-37331601
Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we characterized the lenses from a nonconnexin mutant mouse cataract model. By cosegregation of the phenotype with a satellite marker and genomic sequencing, we identified the mutant as a 5-bp duplication in the γC-crystallin gene (Crygcdup). Homozygous mice developed severe cataracts early, and heterozygous animals developed small cataracts later in life. Immunoblotting studies showed that the mutant lenses contained decreased levels of crystallins, connexin46, and connexin50 but increased levels of resident proteins of the nucleus, endoplasmic reticulum, and mitochondria. The reductions in fiber cell connexins were associated with a scarcity of gap junction punctae as detected by immunofluorescence and significant reductions in gap junction-mediated coupling between fiber cells in Crygcdup lenses. Particles that stained with the calcium deposit dye, Alizarin red, were abundant in the insoluble fraction from homozygous lenses but nearly absent in wild-type and heterozygous lens preparations. Whole-mount homozygous lenses were stained with Alizarin red in the cataract region. Mineralized material with a regional distribution similar to the cataract was detected in homozygous lenses (but not wild-type lenses) by micro-computed tomography. Attenuated total internal reflection Fourier-transform infrared microspectroscopy identified the mineral as apatite. These results are consistent with previous findings that loss of lens fiber cell gap junctional coupling leads to the formation of calcium precipitates. They also support the hypothesis that pathologic mineralization contributes to the formation of cataracts of different etiologies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article