Effects of the genetic background on cognitive performances of TG2576 mice

Animal models of genetic diseases obtained by transferring human mutated genes in the mouse are widely used in biomedical based research. They constitute efficient tools to study mechanisms underlying abnormal phenotypes. Unfortunately, the phenotype of the transgene is often obscured by the genetic background of the embryonic stem cells and that of the recipient strain used to create the transgenic line. It is also known, from the literature, that repeatedly backcrossing a transgenic strain to an inbred background may have unfavorable effects that can result in the loss of the transgenic line. In order to analyze the influences of the genetic background on the transgene expression, we studied the effects of the hAPPswe transgene involved in Alzheimer's Amyloid Pathology, in 3 genetic backgrounds differing by their genetic heterogeneity (homozygous vs heterozygous) and the strain of origin (C57BL6, CBA, B6SJL F1) after only one generation backcrossing. Three different behavioral paradigms were used to assess the psychological and cognitive phenotypic differences: elevated plus maze, morris navigation task and contextual fear conditioning. Our data indicate that the best solution to maintain the transgenic line is to backcross repeatedly the transgenic mice into the F1 hybrid cross that was used to create the transgenic strain, whereas phenotyping should be performed comparatively after only one generation backcrossing into various well chosen F1 or inbred backgrounds.