Genetic loci contributing to age-related hippocampal lesions in mice.
C57BL/6J mice develop genetically determined age-related hippocampal granular deposits that have some similarities to lesions seen in the brains of human patients with tau protein related neurodegenerative disorders ("tauopathies"). We sought to identify the genetic loci responsible for these in an F2 intercross of inbred mouse strains C57BL/6J and DBA/2J, using quantitative trait locus (QTL) analysis. Hippocampal lesions were shown to be PAS positive, H and E negative, and immunoreactive for tau protein and alpha synuclein, but not to Abeta 1-40 or Abeta 1-42, or for ubiquitin. These were quantitated by histomorphometry, and QTL analysis revealed a locus on chromosome 7 with a lod score of 6.5 as well as two suggestive loci on chromosome 10. The genomic data indicate that the genetic basis is complex, but with one locus playing a major role in lesion formation. These lesions may represent a useful model for investigating dysregulation of tau protein in the hippocampus.
Krass
Kelly L
KL
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Colinayo
Veronica
V
Ghazalpour
Anatole
A
Vinters
Harry V
HV
Lusis
Aldons J
AJ
Drake
Thomas A
TA
D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000483:Alleles; D010131:Aminosalicylic Acid / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D002875:Chromosomes; D005260:Female; D008040:Genetic Linkage; D006624:Hippocampus / Q000737:chemistry / Q000473:pathology*; D007150:Immunohistochemistry; D008126:Lod Score; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009419:Nerve Tissue Proteins / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D040641:Quantitative Trait Loci; D051843:Synucleins; D024801:Tauopathies / Q000473:pathology; D051844:alpha-Synuclein; D016875:tau Proteins / Q000032:analysis
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; C098994:amyloid beta-protein (1-43); D016875:tau Proteins; D010131:Aminosalicylic Acid