@article{TEXTUAL,
      recid = {6885},
      author = {Minogue, Peter J. and Gao, Junyuan and Mathias, Richard T.  and Williams, James C.,  Jr. and Bledsoe, Sharon B. and  Sommer, Andre J. and Beyer, Eric C. and Berthoud, Viviana  M.},
      title = {A crystallin mutant cataract with mineral deposits},
      journal = {Journal of Biological Chemistry},
      address = {2023-06-17},
      number = {TEXTUAL},
      abstract = {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  (Crygc<sup>dup</sup>). 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 Crygc<sup>dup</sup> 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. },
      url = {http://knowledge.uchicago.edu/record/6885},
}