Research Models

APP(V642I)KI

Synonyms: Knock-in of APP(V642I)

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Species: Mouse
Genes: APP
Mutations: APP V717I (London)
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice
Availability: Unknown.

Modification Details

Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system.

Neuropathology

Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.

Cognition/Behavior

At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.

Note

The V642I mutation in APP corresponds to V717I by APP770 numbering.

Phenotype Timeline

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.

Observed

Absent

  • Plaques
  • Tangles
  • Neuronal Loss

Unknown

Plaques

Absent.

Tangles

Absent.

Neuronal Loss

Absent.

Cognitive Impairment

Impairments at the water finding task at age 27-29 months, a test of long-term memory. No differences in the open field test of the elevated plus maze indicating no difference in general behavioral patterns, activity level, or emotional state.

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Further Reading

Papers

  1. . Analysis of neurons created from wild-type and Alzheimer's mutation knock-in embryonic stem cells by a highly efficient differentiation protocol. J Neurosci. 2003 Sep 17;23(24):8513-25. PubMed.