Behavioural performance in three substrains of mouse strain 129

Area of Science:

• Neuroscience
• Behavioral Genetics
• Animal Models

Background:

• Behavioral abnormalities in null-mutant mice are sometimes attributed to genetic background, particularly when using the 129 mouse strain for embryonic stem (ES) cell derivation.
• This raises questions about whether observed deficits stem from gene function loss or inherent strain differences.

Purpose of the Study:

• To investigate the influence of genetic background on behavioral phenotypes in different 129 mouse substrains.
• To determine if specific 129 substrains commonly used for ES cell derivation exhibit behavioral deficits.

Main Methods:

• Comparative behavioral analysis of three 129 mouse substrains (129/J, 129/Ola, 129/Sv-ter/+) and C57BL/6 (B6) mice.
• Assessment using the Morris water maze (spatial learning/memory), open field test (anxiety), plus maze, and motor coordination tests.

Main Results:

• The 129/J substrain exhibited significant behavioral deficits, including impaired spatial learning, memory, and motor coordination, along with higher basal anxiety.
• 129/Ola and 129/Sv-ter/+ substrains performed normally in most tests, including the Morris water maze.
• Crucially, the 129/J substrain was not used as an ES cell donor in reported cases of behavioral abnormalities in null-mutant mice.

Conclusions:

• Behavioral deficits observed in some null-mutant mouse studies may be linked to the specific genetic background of the 129/J substrain, rather than solely to gene function loss.
• The 129/Ola and 129/Sv-ter/+ substrains, commonly used for ES cell derivation, do not appear to introduce significant behavioral confounding factors.
• These findings highlight the importance of carefully considering the genetic background of mouse models in behavioral neuroscience research.