Experiment
Linkage analysis was performed on 123 16-month old female animals from a (C57BL/6J x DBA/2J)F2 intercross to identify QTLs linked to age-related brain lesions. 136 polymorphic loci at an average spacing of 13 cM were genotyped. Granular hippocampal lesions are immunoreactive for tau protein and synuclein and are observed in human neurodegenerative disorders. Parental strain C57BL/6J displays a greater density of brain lesions in aged animals compared to parental strain DBA/2J. At 12 weeks of age animals were placed on a high fat, high cholesterol diet for 16 weeks as part of another study.
Significant linkage mapped to 26 cM on mouse Chromosome 7 near D7Mit91 (LOD=6.5). C57BL/6J-derived alleles confer increased incidence of brain lesions at this locus with a dominant mode of inheritance. This locus is named Gbrln (granular brain lesions). Potential candidate genes mapping near Gbrln are Apba2 (25.5 cM), Bax (23 cM), Syt3 (23 cM), Ndn (28 cM), Ube3a (28.65 cM).
Suggestive linkage was detected on proximal and distal mouse Chromosome 10 at D10Mit15 (35 cM, LOD=4.1) and D10Mit10 (51 cM, LOD=2.6). C57BL/6J-derived alleles confer increased incidence of brain lesions with combined additive and dominance effects at both loci. Potential candidates for the proximal locus include Prep (28.5 cM), Lama2 (20 cM), and Lama4 (25 cM). A candidate for the distal locus is Syt1 (58 cM).