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Characterization of small Maf regulators in lens fiber cell differentiation and cataract formation
Author(s) -
Dang Christine,
Agrawal Smriti A,
Waters Stephanie M,
Motohashi Hozumi,
Lachke Salil A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.874.25
Subject(s) - biology , genetics , crystallin , gene , mutant , microbiology and biotechnology
The MAF (musculoaponeurotic fibrosarcoma) gene family includes “large” and “small” MAF subgroups that encode bZIP transcriptional regulators. Although mutations in the large MAF gene “ MAF ” cause human congenital cataract, function of the small MAF genes MAFF , MAFK , and MAFG in the lens remains uncharacterized. iSyTE (integrated Systems Tool for Eye gene discovery), a tool that identifies genes associated with lens development and cataract, has predicted MAFG as a potential regulator in the lens. To test this prediction, we aimed to characterize mouse models carrying targeted mutant alleles of small Maf genes. In situ hybridization and Western blotting confirmed that Mafg mRNA and protein were expressed in the embryonic and adult mouse lens tissue. Furthermore, Mafg − / − ;Mafk+/ − compound mutant mice exhibit lens defects and develop pre‐senile cataract by age six months. Expression profiling by mouse Illumina microarrays on 2‐month old Mafg − / − ;Mafk+/ − compound mutant and control lenses identified several differentially regulated genes in the lens. This analysis indicates that expression of the heat shock protein gene Hspb1 (also known as Hsp27 ) is significantly down‐regulated in Mafg − / − ;Mafk+/ − compound mutant lenses. Together, these results suggest a functional role for the small Maf proteins MAFG and MAFK in maintenance of lens transparency. This research was funded by a Fight For Sight Foundation grant.