Characterization of Ayu17-449 gene expression and resultant kidney pathology in a knockout mouse model

Abstract

The gene trap technique is a powerful approach for characterizing and mutating genes in the mouse. We used this method to identify a mouse gene of unknown function and to establish a mutant mouse line. We subsequently identified one gene, denoted Ayu17-449, on mouse chromosome 3 that comprised 14 exons encoding 1920 amino acids with a granin motif in its N-terminal sequence. In adult mice, this gene was highly expressed in the brain, heart, lung, muscle, stomach, and kidney. The insertion of a trap vector into the second intron of this gene resulted in the null mutation. Homozygous mice for these mutation died by 1 day after birth. Mutant mice showed a loss of acidic granules in the proximal convoluted tubules of the kidney. Our data demonstrates that Ayu17-449 is important for mouse survival.