Viability of trisomy 12 cells in mouse chimaeras

Summary Mouse aggregation chimaeras consisting of trisomy 12 and normal euploid cells were produced. The analysis of one trisomy 12euploid chimaera, using biochemical and cytological markers, showed that the trisomic cells were able to participate in the formation of most tissues including the ovary. On the other hand, no trisomy 12 cells were found in lymphocyte populations, which is most likely due to early selection in this particular cell lineage. The viability of two adult trisomy 12 chimaeras demonstrates that trisomy 12 cells are able to develop beyond the fetal stage which is not observed in completely trisomic fetuses.Furthermore, these chimaeras did not show any sign of a trisomy 12 syndrome, indicating that the trisomy 12 cells were functionally integrated and participated normally in the differentiation of the various tissues. Our results suggest that trisomy 12 in the mouse is not autonomously cell lethal but can be rescued and is perfectly viable in the presence of normal diploid cells.This article is dedicated to the memory of Prof. A. Gropp     

A novel null allele of mouse DSCAM survives to adulthood on an inbred C3H background with reduced phenotypic variability

DSCAMs are cell adhesion molecules that play several important roles in neurodevelopment. Mouse alleles of Dscam identified to date do not survive on an inbred C57BL/6 background, complicating analysis of DSCAM‐dependent developmental processes because of phenotypic variability related to the segregating backgrounds needed for postnatal survival. A novel spontaneous allele of Dscam, hereafter referred to as Dscam^2J, has been identified. This allele contains a four base pair duplication in exon 19, leading to a frameshift and truncation of the open reading frame. Mice homozygous for the Dscam^2J mutant allele survive into adulthood on the C3H/HeJ background on which the mutation was identified. Using the Dscam^2J allele, retinal phenotypes that have variable severity on a segregating background were examined. A neurite lamination defect similar to that described in chick was discovered in mice. These results indicate that, in the retina, additional DSCAM‐dependent processes can be found by analysis of mutations on different genetic backgrounds. © genesis 48:578–584, 2010. © 2010 Wiley‐Liss, Inc.