Mafa is a basic leucine-zipper containing member of the large Maf transcription factor family. It is part of the RIPE3b1 activator complex and functions as a key activator of insulin and pdx-1 gene transcription. Mafa^lox mice may be used to generate both global and cell-specific Mafa null mice, depending on which cre-expressing transgenic mouse is used. Removal of Mafa gene might have a profound effect on beta cell function; thus we can closely monitor the expression of islet hormones, transcription functions and the glucose sensing machinery immunohistochemically. The experiment will provide us with the information about the role of Mafa plays in vivo in islet beta cells and the developing pancreas, thus helping us to understand how transcription activator contribute to the pathogenesis and the treatment of diabetes

The targeting vector is FRT.loxP that utilizes both the Cre/Lox and Flpe/FRT recombinase systems. It contains a phosphoglycerol kinase-neomycin (pgk-neo) resistance gene cassette(neoR) for positive ES cell selection, a pgk-thymidine kinase (pgk-tk) cassette for negative ES cell selection, a 1.723 kb short arm gene fragment, a 4.905 kb long arm fragment, and the 2.354 kb target region (coding sequence plus 1106 bp upstream sequence and 170 bp downstream sequence) in the Mafa gene. Two tandemly oriented loxP sites flank the target region to allow for Cre-recombinase deletion studies; and two tandemly oriented FRT sites flank the neoR for Flip-recombinase deletion of neoR cassette. The backbone vector is pBluescript KS+. This strain allows for the global and tissue specific knock-out of Mafa gene. For example, crossing the Mafa^lox/lox mice with an insulin-cre transgenic mouse generates a beta cell specific knock-out of Mafa.

PMID: 20627934