Dataset Information

Analysis of mouse lens morphological and proteomic abnormalities following depletion of the betaB3-crystallin

ABSTRACT: Crystallin proteins serve as both essential structural and protective components of the ocular lens required for its transparency and light refraction. The mouse lens crystallin proteome is represented by alphaA-, alphaB-, betaA1-, betaA2-, betaA3-, betaA4-, betaB1-, betaB2-, betaB3-, gammaA-, gammaB-, gammaC-, gammaD-, gammaE, gammaF-, gammaN-, and gammaS-crystallin proteins encoded by 16 genes. Their mutations are responsible for lens opacification and early onset cataract formation. While many cataract-causing missense and nonsense mutations are known for these proteins, including the human CRYBB3 gene, the mammalian loss-of function model of the Crybb3 gene remains to be established. Herein, we generated the first mouse model via deletion of the Crybb3 promoter that abolished expression of the betaB3-crystallin resulting in disrupted lens morphology with initial phenotypic variability. The lens morphology was evaluated at histological levels and in-depth lens proteomes were analyzed using newborn, 3-week, 6-week, and 3-month-old lenses. These Crybb3-null lens proteomes showed both down- and up-regulation of various cytoplasmic and nuclear proteins with the largest differences found in 3-months lenses. Expression of Smarcc1/Baf155, b, and c proteins were validated by western immunoblotting/immunofluorescence. The betaB3-crystallin promoter region contain multiple binding sites of transcription factors AP-2a, c-Jun, c-Maf, Etv5, and Pax6, and is activated by FGF2 in cell culture experiments. Together, these studies establish the mouse Crybb3 loss-of-function model and its disrupted crystallin and non-crystallin proteomes.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lens

SUBMITTER: Phillip Wilmarth

LAB HEAD: Ales Cvekl

PROVIDER: PXD059220 | Pride | 2025-09-01

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	CVEK-1210_Fusion_Semi_peptide_results_9.txt	Txt
	CVEK-1210_MouseLens_TMT16_2DRPRP_50ug_PSRtrapPSRcol_140m_17pc_20230711_OT.raw	Raw
	CVEK-1210_MouseLens_TMT16_2DRPRP_50ug_PSRtrapPSRcol_140m_17pc_20230711_OT_filtered.ms2	Other
	CVEK-1210_MouseLens_TMT16_2DRPRP_50ug_PSRtrapPSRcol_140m_17pc_20230711_OT_filtered.sqt	Other
	CVEK-1210_MouseLens_TMT16_2DRPRP_50ug_PSRtrapPSRcol_140m_17pc_20230711_OT_filtered.txt	Txt

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Analysis of mouse lens morphological and proteomic abnormalities following deletion of the βB3-crystallin promoter.

Rayêe Danielle D Wilmarth Phillip A PA VanSlyke Judy K JK Zientek Keith K Reddy Ashok P AP Musil Linda S LS David Larry L LL Cvekl Aleš A

Experimental eye research 20250819

Crystallin proteins serve as both essential structural and as well as protective components of the ocular lens and are required for the transparency and light refraction properties of the organ. The mouse lens crystallin proteome is represented by αA-, αB-, βA1-, βA2-, βA3-, βA4-, βB1-, βB2-, βB3-, γA-, γB-, γC-, γD-, γE, γF-, γN-, and γS-crystallin proteins encoded by 16 genes. Their mutations are responsible for lens opacification and early onset cataract formation. While many cataract-causing ...[more]

PMID: 40840647

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