Spontaneous microdeletions and microinsertions in a transgenic mouse mutation detection system: Analysis of age, tissue, and sequence specificity

A total of 3497 independent spontaneous mutations were examined using the B ig Blue((R)) transgenic mouse mutation detection system. Base substitutions predominate, although 16% of somatic and germline mutations are microdelet ions, micro-insertions, or deletions combined with insertions. The pattern of microdeletions and microinsertions is similar in both the lad transgene and the human p53 gene. Single-base deletions (D1) and insertions (11) are evenly distributed in the lad transgene, whereas microdeletions from 2 to 5 0 bp are clustered at two regions (bp 529-628 and 529-628). The pattern of microdeletions and microinsertions is similar between young (less than or e qual to3 months) and old (25 months) mice. Brain tissue has a paucity of de letions combined with insertions when compared with that of thymus and nine other tissues (P = 0.01). A 16-bp deletion at lacl base position 272 is a tissue-specific hotspot preferentially occurring in brain. Approximately 68 and 93% of D1 and II, respectively, occur at mononucleotide repeats. The f requencies of D1 and Il in mononucleotide repeats increase in an exponentia l manner with the length of the repeat. The loci transgene shows similarity to the human p53 gene in the pattern of microdeletions and microinsertions and the size distribution of microdeletions. (C) 2001 Wiley-Liss, Inc.