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 D. Greenberg; Robert Siman; Mark E. Swanson; Richard W. Scott

doi:10.1016/0197-4580(95)00078-S

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 D. Greenberg, Robert Siman, Mark E. Swanson, Richard W. Scott

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	685-699
Number of pages	15
Journal	Neurobiology of aging
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/0197-4580(95)00078-S
State	Published - 1995
Externally published	Yes

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

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10.1016/0197-4580(95)00078-S

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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 D.; Siman, Robert; Swanson, Mark E.; Scott, Richard W.

In: Neurobiology of aging, Vol. 16, No. 4, 1995, p. 685-699.

Research output: Contribution to journal › Article › peer-review

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 D. ; 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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title = "Mutant and native human β-amyloid precursor proteins in transgenic mouse brain",

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.",

keywords = "Alzheimer's disease, Synapsin I promoter, Transgenic mice, β-amyloid precursor protein",

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

year = "1995",

doi = "10.1016/0197-4580(95)00078-S",

language = "English (US)",

volume = "16",

pages = "685--699",

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AU - Howland, David S.

AU - Savage, Mary J.

AU - Huntress, Frederick A.

AU - Wallace, Racheal E.

AU - Schwartz, Daniel A.

AU - Loh, Tatjana

AU - Melloni, Richard H.

AU - Degennaro, Louis J.

AU - Greenberg, Barry D.

AU - Siman, Robert

AU - Swanson, Mark E.

AU - Scott, Richard W.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Synapsin I promoter

KW - Transgenic mice

KW - β-amyloid precursor protein

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

Abstract

Keywords

ASJC Scopus subject areas

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