Informatics Center for Mouse Genomics: The Dissection of Complex Traits of the Nervous System

Abstract

In recent years, there has been an explosion in the number of tools and techniques available to researchers interested in exploring the genetic basis of all aspects of central nervous system (CNS) development and function. Here, we exploit a powerful new reductionist approach to explore the genetic basis of the very significant structural and molecular differences between the brains of different strains of mice, called either complex trait or quantitative trait loci (QTL) analysis. Our specific focus has been to provide universal access over the web to tools for the genetic dissection of complex traits of the CNS--tools that allow researchers to map genes that modulate phenotypes at a variety of levels ranging from the molecular all the way to the anatomy of the entire brain. Our website, The Mouse Brain Library (MBL; http://mbl.org) is comprised of four interrelated components that are designed to support this goal: The Brain Library, iScope, Neurocartographer, and WebQTL. The centerpiece of the MBL is an image database of histologically prepared museum-quality slides representing nearly 2000 mice from over 120 strains--a library suitable for stereologic analysis of regional volume. The iScope provides fast access to the entire slide collection using streaming video technology, enabling neuroscientists to acquire high-magnification images of any CNS region for any of the mice in the MBL. Neurocartographer provides automatic segmentation of images from the MBL by warping precisely delineated boundaries from a 3D atlas of the mouse brain. Finally, WebQTL provides statistical and graphical analysis of linkage between phenotypes and genotypes.

Genetic and Structural Analysis of the Basolateral Amygdala Complex in BXD Recombinant Inbred Mice

“…The serial sections used in this study are all part of the Mouse Brain Library (MBL) collection of physical sections. Images of these sections can also be downloaded from http://www.mbl.org Seecharan et al 2003;Rosen et al 2003). The BXD strains are completely inbred and have been generated by the repeated mating between siblings starting from the F2 stage (Taylor 1989;Taylor et al 1999).…”

Developmental changes in spinal motoneuron dendrites in neonatal mice

“…Because of the availability of spontaneous and genetically engineered neurological mutants, the mouse has become a key model species for studies of the influence of specific molecular pathways in the development and maintenance of neuronal dendrites (e.g., Ma and VaccaGalloway, 1991;Inglis et al, 1998Inglis et al, , 2000Inglis et al, , 2002Sun and Oppenheim, 2003; see also Rosen et al, 2003). Although intracellular staining and computer-assisted reconstruction techniques (see Ascoli et al, 2001, for review) have provided a wealth of quantitative details about the morphology of MN dendrites in adult cats and rats (e.g., Cameron et al, 1985;Rose et al, 1985;Cullheim et al, 1987a,b;Moschovakis et al, 1991;Ramirez and Ulfhake, 1992;Chen and Walpow, 1994), there is much less quantitative information about the dendrites of mouse MNs.…”

Image registration using threefold orthogonal wavelet

“…From each test brain, a coronal section located in the olfactory bulbs was extracted together with its corresponding section in the atlas brain. This matching of a reference section to its test section was done manually using the MacOStat software package [14,15]. Figure 2 shows one pair of reference and corresponding test sections.…”