Generation of a new mouse model of glaucoma characterized by reduced expression of the AP-2β and AP-2δ proteins

Maria Monica Barzago, Mami Kurosaki, Maddalena Fratelli, Marco Bolis, Chiara Giudice, Laura Nordio, Elisa Cerri, Luciano Domenici, Mineko Terao, Enrico Garattini

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Abstract

We generated 6 transgenic lines with insertion of an expression plasmid for the R883/M xanthine dehydrogenase (XDH) mutant protein. Approximately 20% of the animals deriving from one of the transgenic lines show ocular abnormalities and an increase in intra-ocular pressure which are consistent with glaucoma. The observed pathologic phenotype is not due to expression of the transgene, but rather the consequence of the transgene insertion site, which has been defined by genome sequencing. The insertion site maps to chromosome 1qA3 in close proximity to the loci encoding AP-2β and AP-2δ, two proteins expressed in the eye. The insertion leads to a reduction in AP-2β and AP-2δ levels. Down-regulation of AP-2β expression is likely to be responsible for the pathologic phenotype, as conditional deletion of the Tfap2b gene in the neural crest has recently been shown to cause defective development of the eye anterior segment and early-onset glaucoma. In these conditional knock-out and our transgenic mice, the morphological/histological features of the glaucomatous pathology are surprisingly similar. Our transgenic mouse represents a model of angle-closure glaucoma and a useful tool for the study of the pathogenesis and the development of innovative therapeutic strategies.

Original languageEnglish
Article number11140
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Transgenes
Glaucoma
Transgenic Mice
Eye Abnormalities
Xanthine Dehydrogenase
Anterior Eye Segment
Phenotype
Angle Closure Glaucoma
Neural Crest
Gene Deletion
Mutant Proteins
Proteins
Plasmids
Down-Regulation
Chromosomes
Genome
Pathology
Pressure
Therapeutics
Early-Onset Glaucoma

ASJC Scopus subject areas

  • General

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Generation of a new mouse model of glaucoma characterized by reduced expression of the AP-2β and AP-2δ proteins. / Barzago, Maria Monica; Kurosaki, Mami; Fratelli, Maddalena; Bolis, Marco; Giudice, Chiara; Nordio, Laura; Cerri, Elisa; Domenici, Luciano; Terao, Mineko; Garattini, Enrico.

In: Scientific Reports, Vol. 7, No. 1, 11140, 01.12.2017.

Research output: Contribution to journalArticle

Barzago, Maria Monica ; Kurosaki, Mami ; Fratelli, Maddalena ; Bolis, Marco ; Giudice, Chiara ; Nordio, Laura ; Cerri, Elisa ; Domenici, Luciano ; Terao, Mineko ; Garattini, Enrico. / Generation of a new mouse model of glaucoma characterized by reduced expression of the AP-2β and AP-2δ proteins. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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