Genetic and hereditary influences that give rise to variation in the magnitude and direction of lateralization are presently the least understood processes in the etiology of cerebral dominance. Because the mice exhibit marked asymmetries that are analogous, if not prototypic to the expressed functional asymmetries of human beings, and because the knowledge of the genetics of the mouse is far more advanced than that of any other mammal, studies of the hereditary bases of lateralization in mice can make unique contributions to an understanding of lateralization of the nervous system. The objective of this research is to gain increased knowledge of the genetic, hereditary, developmental and neurobiological processes leading to the variability in the expression of brain/behavioral asymmetry in genetically defined and definable strains and stocks of mice. The long-term goal is to create and characterize practical experimental models of variable lateralization that will be useful for understanding normative processes as well as specific behavioral differences, deficits and associated pathology arising from anomalous patterns of lateralization in humans. A unique mammalian genetic resource for these studies is being developed following eleven generations of directional selective breeding. The HI and LO lines differ from each other in degree of asymmetry, as well as from intermediate lateralization expressed by the HET reference population. In addition, three panels of incipient inbred strains are being developed from the selected lines and their crosses to provide resources for studies of complex genetic-environment interactions. Specific research aims during the next project period are (a) to assess divergence between HI, LO, and HET control lines following 3 additional generations of reimpressed selections; (b) to continuously monitor degree of lateralization between lines; (c) to continue to develop the panel of incipient inbred strains derived for the HI, LO lines and their crosses; (d) to initiate genetic and behavioral characterization of these inbred strains; (e) to test the hypothesis that H-2 associated genes affect variable brain/behavioral asymmetry in experiments using panels of H-2 congenic mice; and (f) to actively pursue studies on the neurobiological mechanisms underlying the observed differences of brain/behavioral asymmetry through collaborative efforts with other neuroscientists who bring special expertise to the study of cerebral lateralization.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023618-10
Application #
3271789
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-06-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
Reid, H M; Collins, R L (1993) Recovery of susceptibility to audiogenic seizure in mice. Epilepsia 34:18-23
Collins, R L; Sargent, E E; Neumann, P E (1993) Genetic and behavioral tests of the McManus hypothesis relating response to selection for lateralization of handedness in mice to degree of heterozygosity. Behav Genet 23:413-21
Bulman-Fleming, B; Wainwright, P E; Collins, R L (1992) The effects of early experience on callosal development and functional lateralization in pigmented BALB/c mice. Behav Brain Res 50:31-42
Reid, H M; Collins, R L (1992) Monaural audiogenic seizures: evidence for control by parallel processes. Epilepsia 33:785-8
Neumann, P E; Collins, R L (1992) Confirmation of the influence of a chromosome 7 locus on susceptibility to audiogenic seizures. Mamm Genome 3:250-3
Gruber, D; Waanders, R; Collins, R L et al. (1991) Weak or missing paw lateralization in a mouse strain (I/LnJ) with congenital absence of the corpus callosum. Behav Brain Res 46:9-16
Collins, R L (1991) Reimpressed selective breeding for lateralization of handedness in mice. Brain Res 564:194-202
Neumann, P E; Collins, R L (1991) Genetic dissection of susceptibility to audiogenic seizures in inbred mice. Proc Natl Acad Sci U S A 88:5408-12
Cassells, B; Collins, R L; Wahlsten, D (1990) Path analysis of sex difference, forebrain commissure area and brain size in relation to degree of laterality in selectively bred mice. Brain Res 529:50-6
Ward, R; Collins, R L; Tanguay, G et al. (1990) A quantitative study of cerebrovascular variation in inbred mice. J Anat 173:87-95

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