PXD059220-1

PXD059220 is an original dataset announced via ProteomeXchange.

Title	Analysis of mouse lens morphological and proteomic abnormalities following depletion of the betaB3-crystallin
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-09-01
AnnouncementXML	Submission_2025-08-31_16:57:04.758.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-24 13:38:40	ID requested
⏵ 1	2025-08-31 16:57:05	announced

10.1016/j.exer.2025.110587;

submitter keyword: cytoplasm, isobaric labeling, cataract, proteomes,betaB3-crystallin, lens, quantitative proteomics

Ales Cvekl
contact affiliation	Departments of Ophthalmology and Visual Sciences and Genetics Albert Einstein College of Medicine Bronx, New York 10461 USA
contact email	ales.cvekl@einsteinmed.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059220
     1. Label: PRIDE project
     2. Name: Analysis of mouse lens morphological and proteomic abnormalities following depletion of the betaB3-crystallin