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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-12-22
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pubmed:abstractText |
FE65 is a multimodular adapter protein that is expressed predominantly in brain. Its C-terminal phosphotyrosine interaction domain (PID) binds to the intracellular tail of the beta-amyloid precursor protein (betaPP), a protein of central importance to the pathogenesis of dementias of the Alzheimer type. To study the physiological functions of FE65, we generated a line of FE65 knockout mice via gene targeting. By Western analysis with a panel of FE65-specific antibodies, we demonstrate that the 97-kDa full-length FE65 (p97) was ablated in the mutant mice, and that a previously undescribed FE65 isoform with apparent molecular mass of 60 kDa (p60) was expressed in both wild-type and mutant mice. p60 had a truncated N-terminus and was likely to be generated through alternative translation. Expressions of the two isoforms appeared to be brain region distinct and age dependent. The p97FE65(-/-) mice were viable and showed no obvious physical impairments or histopathological abnormalities. However, p97FE65(-/-) and p97FE65(+/-) mice exhibited poorer performances than wild-type mice on a passive avoidance task when tested at 14 months (P <.05). p97FE65(-/-) mice at 14 months also exhibited impaired hidden-platform acquisition (P <.05) and a severe reversal-learning deficit (P <.002) but normal visual-platform acquisition in the Morris water maze tests. Probe trials confirmed impairments in p97FE65(-/-) mice in relearning of new spatial information, suggesting a hippocampus-dependent memory-extinction deficit. Reduced secretion of Abeta peptides was observed in primary neuronal cultures of hybrids of p97FE65(-/-)/betaPP transgenic (Tg2576) mice. These studies suggest an important and novel function of FE65 in learning and memory.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Apbb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Luxol Fast Blue MBS,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-40),
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42)
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12-24
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:14689444-Aging,
pubmed-meshheading:14689444-Amyloid beta-Peptides,
pubmed-meshheading:14689444-Analysis of Variance,
pubmed-meshheading:14689444-Animals,
pubmed-meshheading:14689444-Animals, Newborn,
pubmed-meshheading:14689444-Avoidance Learning,
pubmed-meshheading:14689444-Behavior, Animal,
pubmed-meshheading:14689444-Blotting, Northern,
pubmed-meshheading:14689444-Blotting, Western,
pubmed-meshheading:14689444-Brain,
pubmed-meshheading:14689444-Cells, Cultured,
pubmed-meshheading:14689444-Cerebral Cortex,
pubmed-meshheading:14689444-Electroshock,
pubmed-meshheading:14689444-Female,
pubmed-meshheading:14689444-Indoles,
pubmed-meshheading:14689444-Male,
pubmed-meshheading:14689444-Maze Learning,
pubmed-meshheading:14689444-Memory Disorders,
pubmed-meshheading:14689444-Mice,
pubmed-meshheading:14689444-Mice, Knockout,
pubmed-meshheading:14689444-Molecular Structure,
pubmed-meshheading:14689444-Motor Activity,
pubmed-meshheading:14689444-Nerve Tissue Proteins,
pubmed-meshheading:14689444-Nuclear Proteins,
pubmed-meshheading:14689444-Peptide Fragments,
pubmed-meshheading:14689444-Protein Isoforms,
pubmed-meshheading:14689444-Psychomotor Performance,
pubmed-meshheading:14689444-RNA, Messenger,
pubmed-meshheading:14689444-Reaction Time,
pubmed-meshheading:14689444-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:14689444-Swimming,
pubmed-meshheading:14689444-Time Factors,
pubmed-meshheading:14689444-Transfection,
pubmed-meshheading:14689444-Vocalization, Animal
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pubmed:year |
2004
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pubmed:articleTitle |
Isoform-specific knockout of FE65 leads to impaired learning and memory.
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pubmed:affiliation |
Department of Pathology, University of Washington, Seattle, Washington 98195-7470, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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