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 τ protein related neurodegenerative disorders (“tauopathies”). We sought to identify the genetic loci responsible for these in an F2...

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Bibliographic Details
Published in:Neurobiology of disease 2003-07, Vol.13 (2), p.102-108
Main Authors: Krass, Kelly L, Colinayo, Veronica, Ghazalpour, Anatole, Vinters, Harry V, Lusis, Aldons J, Drake, Thomas A
Format: Article
Language:English
Subjects:
Aging - genetics
Aging - pathology
Alleles
alpha-Synuclein
Aminosalicylic Acid - analysis
Amyloid beta-Peptides - analysis
Animals
Chromosomes
Female
Genetic Linkage
Hippocampus - chemistry
Hippocampus - pathology
Immunohistochemistry
Lod Score
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Nerve Tissue Proteins - analysis
Neurodegenerative brain lesions
Peptide Fragments - analysis
Quantitative Trait Loci
Quantitative trait locus
Synucleins
tau Proteins - analysis
Tauopathies - pathology
τ protein
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Summary: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 τ 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 τ protein and α synuclein, but not to Aβ 1-40 or Aβ 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 τ protein in the hippocampus.
ISSN:0969-9961
1095-953X
DOI:10.1016/S0969-9961(03)00034-2