Behavioral and neuroanatomical characterization of FVB/N inbred mice

doi:10.1016/S0361-9230(01)00635-9

Brain Research Bulletin

Volume 57, Issue 1, 1 January 2002, Pages 41-47

https://doi.org/10.1016/S0361-9230(01)00635-9 Get rights and content

Abstract

The inbred strain FVB/N is becoming increasingly popular to generate transgenic animals. We compared animals from this strain with well-characterized C57BL/6J animals on four different behavioral tests: the elevated plus maze test of anxiety, a standard opponent aggression test, the open-field test, and spatial learning in a radial maze. Our results indicate that FVB/N animals have slightly higher levels of anxiety and aggression, are hyperactive, and have a clear learning deficit. The latter finding seems to be related to an exceptionally small intrapyramidal and infrapyramidal mossy fiber projection. It is recommended that transgenic experiments employing this strain use F1 crosses between FVB/N and C57BL/6J as much as possible for behavioral experiments intended to evaluate spatial learning.

Introduction

In the last 10 years, transgenic and knock-out techniques have become popular tools to investigate the genetic processes underlying many different characteristics. For technical reasons, such as appropriate egg cells that are easy to inject or the availability of embryonic stem cell (ES) lines, most of the mouse models developed to date were created using only a small number of inbred strains. Lately, it was reported that mice from the FVB/N inbred strain have several desirable features that would render them suitable subjects for transgenic experiments [29]. However, until it started to become popular for the generation of transgenic animals, this strain was used only rarely, if ever, by behavioral neurogeneticists, and many aspects of its behavior or central nervous system have not yet been investigated in detail.

Recently, two groups investigated some behavioral and neural phenotypes of FVB animals. Royle et al. [25] reported impaired learning in both a spatial and a visually cued water navigation task (“Morris maze”) and the most severe seizure response and mortality rate (62%) after administration of kainic acid when compared with some other inbred strains, such as C57BL/6J. In FVBs, kainic acid administration also led to higher cell loss in hippocampal CA3. Voikar et al. [30] also reported decreased learning capabilities in both spatial and visually cued versions of the Morris task, as well as hyperactive behavior in an open field. The learning impairment in the water navigation task was accompanied by strongly increased levels of thigmotaxis (“wall-hugging”). Because of this, it is not clear whether this impairment is caused by cognitive deficits or to noncognitive factors [34]. However, both groups also reported deficits in the visually cued version of this task. Indeed, FVB/N animals carry the rd mutation [29], which causes retinal degeneration. Although animals carrying this mutation will not yet be blind at the ages that Royle et al. and Voikar et al. tested their subjects (3–4 months) 11, 15, 20, 21, 22, they will nevertheless be visually strongly impaired, which may explain (part of) the deficits found by these authors.

We decided to investigate several behavioral features of this strain, such as anxiety, aggression, exploratory behavior, and spatial learning in a radial maze. As a comparison, we used the well-documented C57BL/6J strain, which is one of the most used in behavioral neuroscience. In addition, we examined their hippocampal neuroanatomy, in particular, the mossy fiber projections. We have found previously that the extent of a part of this projection, the intrapyramidal and infrapyramidal mossy fibers (IIPMF) is correlated with several of the above-mentioned behaviors (spatial radial-maze learning [26], exploratory behavior [8], and aggression 13, 28). We selected the radial maze, rather than the much used water-navigation task, which is stressful for mice [12]. The radial maze as used in our laboratory minimizes stress and, in addition, poses much lower requirements to the subject’s visual system, as visual cues are much closer than in the Morris task [5].

Section snippets

Animals

FVB/N and C57BL/6J male mice were reared in our SPF animal facility approved by the French Ministry of Agriculture. Males were weaned at 28 days ± 1 of age and housed singly with a companion female (generally a littermate), to avoid excessive fighting between littermates, but limiting isolation stress, under the following conditions: cages 23 cm × 17 cm × 14 cm, temperature 20–22°C; lights on at 7:30 am with a 12:12 light/dark cycle, and water and food available ad libitum. Cages were cleaned

Results

Results from the elevated plus maze are presented in Fig. 1. FVB/N mice exhibit significant differences compared with C57BL/6J mice in almost all of the variables assessed, except for the number of entries in the open arms (absolute: z = 1.21, p = 0.23; percentage of total entries: z = 1.60, p = 0.11). Otherwise, these animals present a significant decrease in the time spent in the open arms when compared with the mice of the C57BL/6J strain, both when measured absolutely (z = 2.25, p < 0.03),

Discussion

The results obtained in the plus-maze test are somewhat ambiguous, as different results were obtained for variables classically associated with anxiety 4, 24. FVB/N animals showed more entries into the open arms than did C57BL/6Js, but as a percentage of total arm entries, their mean value was lower. However, neither of these differences reached significance. The time spent in the open arms was significantly decreased, both in absolute values and relative to the total time spent in any arms.

Acknowledgements

Supported by the 5th Framework Programme of the European Community, Grant QLK6-1999-02189. We thank Dr. David P. Wolfer (Zurich, Switzerland) for generously providing his NIH Image macros and Dr. Yann Herault (Orléans, France) for putting his image analyzer to our disposition.

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Behavioral and neuroanatomical characterization of FVB/N inbred mice

Abstract

Introduction

Section snippets

Animals

Results

Discussion

Acknowledgements

Brain Res.

Brain Res.

Behav. Brain Res.

Brain Res.

Brain Res.

Cogn. Brain Res.

Curr. Opin. Neurobiol.

Brain Res.

Neurosci. Lett.

J. Neurosci. Meth.

Brain Res.

Neuroscience

Brain Res.