Mutant and native human β-amyloid precursor proteins in transgenic mouse brain

David S. Howland, Mary J. Savage, Frederick A. Huntress, Racheal E. Wallace, Daniel A. Schwartz, Tatjana Loh, Richard H. Melloni, Louis J. Degennaro, Barry Greenberg, Robert Siman, Mark E. Swanson, Richard W. Scott

Research output: Contribution to journalArticle

Abstract

Human β-amyloid precursor protein (βAPP) has been targeted to transgenic neurons using synapsin I promoter-based chimeric transgenes. Native human βAPP was introduced as well as βAPP containing mutations genetically linked to familial Alzheimer's disease (AD) and to hereditary cerebral hemorrhage with amyloidosis-Dutch type. In mouse brain, human βAPP RNA was up to 60% as abundant as total endogenous βAPP RNA. Human βAPP gene expression was most abundant in the CA subfields of the hippocampus and in the piriform cortex. Correct processing of human βAPP at the β-secretase cleavage site was demonstrated in transgenic mouse brains. Despite a 40% increase in total βAPP immunoreactivity in lines expressing mutant human βAPP, no evidence of amyloid deposition was found in brains of mice up to 14 months in age. Higher levels of mutant human βAPP, increased age, or other factors may be necessary to elicit β-amyloid-related neuropathologies in the rodent brain.

Original languageEnglish (US)
Pages (from-to)685-699
Number of pages15
JournalNeurobiology of Aging
Volume16
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Population Groups
Transgenic Mice
Brain
Amyloid
RNA
Synapsins
Amyloid Precursor Protein Secretases
Transgenes
Rodentia
Hippocampus
Alzheimer Disease
Gene Expression
Neurons
Mutation

Keywords

  • Alzheimer's disease
  • Synapsin I promoter
  • Transgenic mice
  • β-amyloid precursor protein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Howland, D. S., Savage, M. J., Huntress, F. A., Wallace, R. E., Schwartz, D. A., Loh, T., ... Scott, R. W. (1995). Mutant and native human β-amyloid precursor proteins in transgenic mouse brain. Neurobiology of Aging, 16(4), 685-699. https://doi.org/10.1016/0197-4580(95)00078-S

Mutant and native human β-amyloid precursor proteins in transgenic mouse brain. / Howland, David S.; Savage, Mary J.; Huntress, Frederick A.; Wallace, Racheal E.; Schwartz, Daniel A.; Loh, Tatjana; Melloni, Richard H.; Degennaro, Louis J.; Greenberg, Barry; Siman, Robert; Swanson, Mark E.; Scott, Richard W.

In: Neurobiology of Aging, Vol. 16, No. 4, 01.01.1995, p. 685-699.

Research output: Contribution to journalArticle

Howland, DS, Savage, MJ, Huntress, FA, Wallace, RE, Schwartz, DA, Loh, T, Melloni, RH, Degennaro, LJ, Greenberg, B, Siman, R, Swanson, ME & Scott, RW 1995, 'Mutant and native human β-amyloid precursor proteins in transgenic mouse brain', Neurobiology of Aging, vol. 16, no. 4, pp. 685-699. https://doi.org/10.1016/0197-4580(95)00078-S
Howland DS, Savage MJ, Huntress FA, Wallace RE, Schwartz DA, Loh T et al. Mutant and native human β-amyloid precursor proteins in transgenic mouse brain. Neurobiology of Aging. 1995 Jan 1;16(4):685-699. https://doi.org/10.1016/0197-4580(95)00078-S
Howland, David S. ; Savage, Mary J. ; Huntress, Frederick A. ; Wallace, Racheal E. ; Schwartz, Daniel A. ; Loh, Tatjana ; Melloni, Richard H. ; Degennaro, Louis J. ; Greenberg, Barry ; Siman, Robert ; Swanson, Mark E. ; Scott, Richard W. / Mutant and native human β-amyloid precursor proteins in transgenic mouse brain. In: Neurobiology of Aging. 1995 ; Vol. 16, No. 4. pp. 685-699.
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