Developmental mosaicism may explain spontaneous reappearance of the Axin(Fu) mutation in mice

The Axin(Fu) mutation is caused by an IAP insertion. In a small percentage of mice, the Axin(Fu) mutation disappears and is not observed in the next generation. In these mice, [Axin(Fu)]/+, the IAP is absent and Axin(Fu) has reverted to the wild allele. Concomitantly with the loss of IAP, there is widespread reorganisation of numerous microsatellite loci across the surrounding region of chromosome. In rare cases, spontaneous reappearance of the mutation can be observed in progeny of [Axin(Fu)]/+ mice. It is revealed here that reappearance of Axin(Fu) was associated with restoration of the IAP insertion. In such mice, alleles of the surrounding microsatellite loci were identical to the alleles observed on chromosomes that carried Axin(Fu). Developmental mosaicism can potentially explain spontaneous reappearance of the Axin(Fu) mutation. Mosaicism can also explain other observations including postnatal changes at the Axin locus, unusual segregation in progeny, and the appearance of [Axin(Fu)]/+ mice that were phenotypically mutant. 2001.