Genetic loci contributing to age-related hippocampal lesions in mice

Autor: Kelly L Krass, Veronica Colinayo, Anatole Ghazalpour, Harry V Vinters, Aldons J Lusis, Thomas A Drake
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Zdroj: Neurobiology of Disease, Vol 13, Iss 2, Pp 102-108 (2003)
Druh dokumentu: article
ISSN: 1095-953X
0969-9961
DOI: 10.1016/S0969-9961(03)00034-2
Popis: 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.
Databáze: Directory of Open Access Journals
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