Genetic and behavioral differences among five inbred mouse strains commonly used in the production of transgenic and knockout mice

Abstract

Five strains of mice commonly used in transgenic and knockout production were compared with regard to genetic background and behavior. These strains were: C57BL/6J, C57BL/6NTac, 129P3/J (formerly 129/J), 129S6/SvEvTac (formerly 129/SvEvTac) and FVB/NTac. Genotypes for 342 microsatellite markers and performance in three behavioral tests (rotorod, open field activity and habituation, and contextual and cued fear conditioning) were determined. C57BL/6J and C57BL/ 6NTac were found to be true substrains; there were only 12 microsatellite differences between them. Given the data on the genetic background, one might predict that the two C57BL/6 substrains should be very similar behaviorally. Indeed, there were no significant behavioral differences between C57BL/6J and C57BL/6NTac. Contrary to literature reports on other 129 strains, 129S6/ SvEvTac often performed similarly to C57BL/6 strains, except that it was less active. FVB/NTac showed impaired rotorod learning and cued fear conditioning. Therefore, both 129S6/SvEvTac and C57BL/6 are recommended as background strains for targeted mutations when researchers want to evaluate their mice in any of these three behavior tests. However, any transgene on the FVB/NTac background should be transferred to B6.Habituation to the open field was analyzed using the parameters: total distance, center distance, velocity and vertical activity. Contrary to earlier studies, we found that all strains habituated to the open field in at least two of these parameters (center distance and velocity).

Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades

“…A study of 1,638 single-nucleotide polymorphisms observed that differences among several C57BL͞6 substrains represented residual heterozygosity at the time substrains were separated as well as new mutations (51). Allelic differences at 12 of 342 microsatellite loci were noted between the C57BL͞6J and C57BL͞6NTac substrains that were separated in 1951, Ͼ150 generations ago (52). A C57BL͞6J mouse from The Jackson Laboratory today will not be identical nucleotide-for-nucleotide to the same strain 50 years ago.…”

Cognitive performance in neurokinin 3 receptor knockout mice

“…Any remaining background from the 129P2/OlaHsd strain could influence the behavioral results strongly and might explain differences observed between the two NK 3 knockout lines. Strain differences between C57Bl6 and 129 lines have been demonstrated to affect performance in active avoidance (Clark et al 2003) and cued fear conditioning (Bothe et al 2004), an essential component of the active avoidance paradigm. Strain differences in performance have also been demonstrated in mice in the Morris water maze.…”

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice

“…the 'Freeze Monitor' system) and image-analyzing systems have been used to automatically measure the freezing behavior 26,[30][31][32] . ImageFZ is an automated image-analyzing system, which produces results comparable to those obtained through human observation, as described below.…”

“…However, this method involves potential problems, such as differences in the observational method, observer biases, and simple quantification mistakes, making it difficult to directly compare the results from independent experimenters and different laboratories. An automated photobeam-based computer measurement system has also been used 26,[30][31][32] . However, this system also presents potential problems in measuring freezing behaviors.…”