Genetic loci contributing to age-related hippocampal lesions in mice

Kelly L Krass; Veronica Colinayo; Anatole Ghazalpour; Harry V Vinters; Aldons J Lusis; Thomas A Drake

Neurobiology of Disease (Jul 2003)

Genetic loci contributing to age-related hippocampal lesions in mice

Kelly L Krass,
Veronica Colinayo,
Anatole Ghazalpour,
Harry V Vinters,
Aldons J Lusis,
Thomas A Drake

Affiliations

Kelly L Krass: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA
Veronica Colinayo: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA
Anatole Ghazalpour: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA
Harry V Vinters: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA
Aldons J Lusis: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA
Thomas A Drake: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, CA 90095, USA

Journal volume & issue: Vol. 13, no. 2
pp. 102 – 108

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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