A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice
- 30 June 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in neurogenetics
- Vol. 11 (1), 53-71
- https://doi.org/10.1007/s10048-009-0203-3
Abstract
Humans with L1 cell adhesion molecule (L1CAM) mutations exhibit X-linked hydrocephalus, as well as other severe neurological disorders. L1-6D mutant mice, which are homozygous for a deletion that removes the sixth immunoglobulin-like domain of L1cam, seldom display hydrocephalus on the 129/Sv background. However, the same L1-6D mutation produces severe hydrocephalus on the C57BL/6J background. To begin to understand how L1cam deficiencies result in hydrocephalus and to identify modifier loci that contribute to X-linked hydrocephalus by genetically interacting with L1cam, we conducted a genome-wide scan on F2 L1-6D mice, bred from L1-6D 129S2/SvPasCrlf and C57BL/6J mice. Linkage studies, utilizing chi-square tests and quantitative trait loci mapping techniques, were performed. Candidate modifier loci were further investigated in an extension study. Linkage was confirmed for a locus on chromosome 5, which we named L1cam hydrocephalus modifier 1 (L1hydro1), \( p = 4.04 \times {10^{ - 11}} \).
Keywords
This publication has 76 references indexed in Scilit:
- The interaction between L1-type proteins and ankyrins - a master switch for L1-type CAM functionCellular & Molecular Biology Letters, 2009
- Convergent extension movements and ciliary function are mediated by ofd1 , a zebrafish orthologue of the human oral-facial-digital type 1 syndrome geneHuman Molecular Genetics, 2008
- Mutations inHydinimpair ciliary motility in miceThe Journal of cell biology, 2008
- The ZebrafishfleerGene Encodes an Essential Regulator of Cilia Tubulin PolyglutamylationMolecular Biology of the Cell, 2007
- The X Chromosome in Quantitative Trait Locus MappingGenetics, 2006
- Pre- and postsynaptic actions of L1-CAM in nicotinic pathwaysMolecular and Cellular Neuroscience, 2006
- Genetics of human hydrocephalusZeitschrift für Neurologie, 2006
- RanBPM is an L1‐interacting protein that regulates L1‐mediated mitogen‐activated protein kinase activationJournal of Neurochemistry, 2005
- A Nonneuronal Isoform of Cell Adhesion Molecule L1: Tissue‐Specific Expression and Functional AnalysisJournal of Neurochemistry, 1996
- Genetic dissection of complex traits: guidelines for interpreting and reporting linkage resultsNature Genetics, 1995