Variation in the cortical area map of C57BL/6J and DBA/2J inbred mice predicts strain identity

Abstract

Background: Recent discoveries suggest that arealization of the mammalian cortical sheet develops in a manner consonant with principles established for embryonic patterning of the body. Signaling centers release morphogens that determine regional growth and tissue identity by regulating regional expression of transcription factors. Research on mouse cortex has identified several candidate morphogens that affect anteroposterior or mediolateral cortical regionalization as well as mitogenesis. Inbred strains of laboratory mice can be exploited to study cortical area map formation if there are significant phenotypic differences with which to correlate gene polymorphism or expression data. Here we describe differences in the cortical area map of two commonly used inbred strains of laboratory mice, C57BL/6J and DBA/2J. Complete cortical hemispheres from adult mice were dissected and stained for the cytochrome oxidase enzyme in order to measure histochemically defined cortical areas.

Results: C57BL/6J has the larger neocortex, relatively larger primary visual cortex (V1), but relatively smaller posterior medial barrel subfield of the primary somatosensory cortex (PMBSF). The sample of C57BL/6J and DBA/2J mice can be discriminated with 90% accuracy on the basis of these three size dimensions.

Conclusion: C57BL/6J and DBA/2J have markedly different cortical area maps, suggesting that inbred strains harbor enough phenotypic variation to encourage a forward genetic approach to understanding cortical development, complementing other approaches.

Figure 1

Flattened mouse cortex stained for cytochrome oxidase. Figure 1 top to bottom shows a typical flattened section of a mouse cortex stained for cytochrome oxidase and the boundaries of neocortex, visual cortex, barrel cortex (PMBSF), somatosensory cortex, and auditory cortex outlined in black.

Figure 2

ANCOVA plot for visual cortex. Figure 2 shows a significant over representation (distance between parallel lines) of visual cortex in C57BL/6J mice.

Figure 3

ANCOVA plot for barrel cortex. Figure 3 shows a significant over representation (distance between parallel lines) of barrel cortex in DBA/2J mice.

Figure 4

Prediction plot for strain identity. Figure 4 plots the predicted probability of each mouse being C57BL/6J by strain from a logistic regression model including neocortex, visual cortex, and barrel cortex areas.

Figure 5

Projection of a rotating plot. Figure 5 is a 2-dimensional projection of a 3-dimensional rotating plot of neocortex, visual cortex, and barrel cortex areas (centered by mean and scaled by standard deviation). The projection shows the separation of strains predicted by the logistic regression model (or equivalent discriminant analysis).