Cloning of novel trinucleotide-repeat (CAG) containing genes in mouse brain

Abstract

CAG trinucleotide repeat (CTR) sequence often appears in mammalian genome including transcription-regulatory protein and homeobox genes. Its expansion is associated with six genetic disorders in human. To identify novel CTR-containing genes expressed in mouse brain, a brain cDNA library was screened using an oligonucleotide, (CTG)10. Eight clones were novel mouse genes and they were sequenced on both strands. The size of the cloned DNA ranged from 0.5 to 2.1 kb. The number of the CAG repeats in the clones ranged from 6 to 25. The inserts of the clones were analyzed for open reading frames and the peptide sequences were used for a GenBank homology search. of the clones, one (CAG-6) shared 13 consecutive identical amino acid residues with the OB-cadherin gene, a member of cadherin family. CAG-14 showed high homology (657 nucleotides identity in 1022 nucleotides; 64%) with the 3'-untranslated region of rat leukocyte common antigen-related (LAR) tyrosine phosphatase receptor. All the 8 clones were originated from mouse DNA as judged by Southern blot analysis of mouse genomic DNA. The expression of the clones in mouse brain was addressed by RT-PCR and 4 clones showed specific expression.