Article

Behavioral differences among C57BL/6 substrains: implications for transgenic and knockout studies.

Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
Journal of neurogenetics (Impact Factor: 1.38). 02/2008; 22(4):315-31. DOI: 10.1080/01677060802357388
Source: PubMed

ABSTRACT Separate breeding colonies of C57BL/6 ("B6") mice maintained at the Jackson Laboratories ("J") and NIH ("N") have led to the emergence of two distinct substrains of C57BL/6 mice: C57BL/6J and C57BL/6N. Molecular genetic studies indicate simple sequence-length polymorphisms, single-nucleotide polymorphisms, and copy-number variants among B6 substrains that may contribute to phenotypic differences. We examined differences in motor coordination, pain sensitivity, and conditional fear in the C57BL/6J strain and three N strains: C57BL/6NCrl (Charles River), C57BL/6NTac (Taconic), and C57BL/6NHsd (Harlan Sprague Dawley). Male C57BL/6J mice demonstrated enhanced motor coordination, as measured by the rotarod assay, markedly enhanced pain sensitivity in two assays of acute thermal nociception (e.g., tail withdrawal and hot plate), and a reduced level of conditional fear. The tail withdrawal result was confirmed in a separate laboratory. We also provide a table reviewing previously reported behavioral differences among various B6 substrains and discuss the significance of environmental differences due to obtaining mice form different vendors. These data may be seen as a potential problem and as a potential opportunity. Great care must be taken when working with mice engineered by using B6 embryonic stem cell lines because control groups, backcrosses, and intercrosses could inadvertently introduce behaviorally significant polymorphic alleles or environmental confounds. On the other hand, deliberate crosses between B6 substrains may provide an opportunity to map polymorphic loci that contribute to variability in a trait on largely homogenous backgrounds, which has the potential to improve mapping resolution and aid in the selection of candidate genes.

Download full-text

Full-text

Available from: Michael Fanselow, Jun 29, 2015
0 Followers
 · 
181 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal models are crucial components in the search for better understanding of the biological bases of psychiatric disorders and for the development of novel drugs. Research, in general, and research with animal models, in particular, relies on the consistency of effects of investigated drugs or manipulations across experiments. In that context, it had been noted that behavioral responses to lithium in ICR (CD-1) mice from Harlan Israel have changed across the last years. To examine this change, the present study compared the effect of lithium treatment in ICR mice from Harlan Israel with the ICR mice from Harlan USA. The mice were treated with chronic oral lithium. Their lithium serum levels were measured and their behavior in the forced swim test (FST) was evaluated. The mice were also treated with [(3)H]-inositol ICV and lithium injection and their frontal cortex [(3)H]-phosphoinositol accumulation was measured. Results show that lithium serum levels in Israeli mice were significantly lower compared with the USA mice, that lithium had no behavioral effect in the Israeli mice but significantly reduced FST immobility time of the USA mice, and that phosphoinositol accumulation was much more strongly affected by lithium in the USA mice compared with the Israeli mice. These results suggest that the Israeli Harlan colony of ICR mice changed significantly from the original ICR colony in Harlan USA and that the differences might be related to absorption or secretion of lithium.
    Pharmacology Biochemistry and Behavior 05/2014; DOI:10.1016/j.pbb.2014.05.007 · 2.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal models are crucial components in the search for better understanding of the biological basis of psychiatric disorders and for the development of novel drugs. Research, in general, and research with animal models, in particular, relies on the consistency of effects of investigated drugs or manipulations across experiments. In that context, it had been noted that behavioral responses to lithium in ICR (CD-1) mice from Harlan Israel have changed across the last years. To examine this change, the present study compared the effect of lithium treatment in ICR mice from Harlan Israel with the ICR mice from Harlan USA. The mice were treated with chronic oral lithium. Their lithium serum levels were measured and their behavior in the forced swim test (FST) was evaluated. The mice were also treated with [3H]-inositol ICV and lithium injection and their frontal cortex [3H]-phosphoinositols accumulation was measured. Results show that lithium serum levels in Israeli mice were significantly lower compared with the USA mice, that lithium had no behavioral effect in the Israeli mice but significantly reduced FST immobility time of the USA mice, and that phosphoinositols accumulation was much more strongly affected by lithium in the USA mice compared with the Israeli mice. These results suggest that the Israeli Harlan colony of ICR mice changed significantly from the original ICR colony in Harlan USA and that the differences might be related to absorption or secretion of lithium.
    Pharmacology Biochemistry and Behavior 01/2014; 124:36–39. · 2.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The presynaptic protein α-synuclein is central to the pathogenesis of α-synucleinopathies. We show that the presence of endogenous mouse α-synuclein leads to higher number of dopaminergic neurons in the substantia nigra of wild-type C57Bl6/J mice compared with C57Bl/6S mice with a spontaneous deletion of the α-synuclein gene or C57Bl6/J mice with a targeted deletion of the α-synuclein gene. This effect of α-synuclein on dopaminergic neuron occurs during development between E10.5 and E13.5 and persists in adult life supporting the involvement of α-synuclein in the development of a subset of dopaminergic neurons.
    Experimental Neurology 08/2013; 248. DOI:10.1016/j.expneurol.2013.07.015 · 4.62 Impact Factor