Changes in relative histone abundance and heterochromatin in αA-crystallin and αB-crystallin knock-in mutant mouse lenses.

Citation
Andley, U. P., et al. “Changes In Relative Histone Abundance And Heterochromatin In Αa-Crystallin And Αb-Crystallin Knock-In Mutant Mouse Lenses.”. Bmc Research Notes, p. 315.
Center Washington University in St Louis
Author Usha P Andley, Brittney N Naumann, Paul D Hamilton, Stephanie L Bozeman
Keywords Cataract, Crystallin, electron microscopy, histones, Mass spec, Mouse lens
Abstract

OBJECTIVE: Understanding the mechanisms of cataract formation is important for age-related and hereditary cataracts caused by mutations in lens protein genes. Lens proteins of the crystallin gene families α-, β-, and γ-crystallin are the most abundant proteins in the lens. Single point mutations in crystallin genes cause autosomal dominant cataracts in multigenerational families. Our previous proteomic and RNAseq studies identified genes and proteins altered in the early stages of cataract formation in mouse models. Histones H2A, H2B, and H4 increase in abundance in αA- and αB-crystallin mutant mouse lenses and in cultured cells expressing the mutant form of αA-crystallin linked with hereditary cataracts.

RESULTS: In this study of histones in mutant lenses, we extracted histones from adult mouse lenses from cryaa-R49C and cryab-R120G mutant knock-in mice. We characterized the histones using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF)-mass spectrometric analysis and gel electrophoresis and characterized the lens nucleus morphology using electron microscopy (EM). The relative abundance of histone H3 protein decreased in lenses from cryaa-R49C mutant mice and the relative abundance of histone H2 increased in these lenses. Electron microscopy of nuclei from cryaa-R49C-homozygous mutant mouse lenses revealed a pronounced alteration in the distribution of heterochromatin.

Year of Publication
2020
Journal
BMC research notes
Volume
13
Issue
1
Number of Pages
315
Date Published
07/2020
ISSN Number
1756-0500
DOI
10.1186/s13104-020-05154-7
Alternate Journal
BMC Res Notes
PMID
32616056