Complementary DNA for the mouse homolog of the human amyloid beta protein precursor

Yamada, Takeshi; Sasaki, Hidetada; Furuya, Hirokazu; Miyata, Takashi; Goto, Ikuo; Sakaki, Yoshiyuki

doi:10.1016/0006-291x(87)90419-0

Cited by 141 publications

(61 citation statements)

References 9 publications

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“…Similar deposits have been detected in aged monkeys, dogs, and polar bears, but rarely have they been found in rats and mice (Selkoe, 1989). The sequences of P-amyloid precursor proteins of mice (Yamada et al, 1987) and rats (Shivers et al, 1988), deduced from cDNA clones, are about 90% similar to the human P-amyloid precursor protein. Three amino acid substitutions are found in the A4 region of rodents.…”

mentioning

confidence: 60%

Human and rodent Alzheimer β‐amyloid peptides acquire distinct conformations in membrane‐mimicking solvents

Ötvös

Szendrei

Lee

et al. 1993

European Journal of Biochemistry

119

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The major constituent of senile plaques (one of the hallmark lesions of Alzheimer's disease) is a 42(43)-amino-acid polypeptide, termed the A4 or /3-amyloid peptide. The B-amyloid peptide or A4 is derived from one or more larger P-amyloid precursor proteins. The precursor protein from whence the A4 peptide is derived is highly conserved throughout evolution, and humans, monkeys, dogs, and bears develop brain deposits of A4 peptide in amyloid fibrils. However, similar accumulations of A4 amyloid are negligible in the brains of rats and mice for reasons that remain unexplored. Notably, the A4 sequence of rodents, deduced from the cDNA clones, differs only in three amino acids from the A4 isolated from the brain of humans. Hence, these differences could account for the inability of rodents to develop Alzheimer-like A4 amyloid plaques. To test this hypothesis directly, using physical and chemical model systems, we synthesized, purified, and characterized A4 peptides corresponding to the human and rodent sequences. Circular dichroic and Fourier-transform infrared spectroscopy were used with various membrane-mimicking solvents, different peptide concentrations, and variable pH to identify those environmental conditions that promoted B-pleated sheet formation of the human versus rodent A4. At an intermediate alkaline pH (< lo), the rodent peptide has more P-pleated sheet structure than the human sequence. The /I-pleated sheets for both peptides could be eliminated at very high pH ( 2 12). The amount of the p-structure increasedin an octyl glucoside solution, compared to that found in SDS, as well as in several of the other solutions tested here. This suggests that particles originated from prior membrane damage may play a role in the stabilization of /3-pleated sheets with subsequent formation of amyloid deposits. Finally, we found that higher P-pleated sheet content was observed for the rodent sequences in acetonitrile/water mixtures. In contrast, more P-

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mentioning

confidence: 60%

Human and rodent Alzheimer β‐amyloid peptides acquire distinct conformations in membrane‐mimicking solvents

Ötvös

Szendrei

Lee

et al. 1993

European Journal of Biochemistry

119

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Section: Introductionmentioning

confidence: 83%

“…Total APP expression is highest in the brain (6); APP695 is expressed predominantly in neurons (15), whereas APP751 and APP770 have been detected in every adult tissue examined (6). In the mouse, only splicing forms corresponding to APP695, APP751, and APP770 have been described, and the tissue distributions of these three forms are similar to that seen in human beings (16,17).Both abnormal levels of APP expression and aberrant splicing regulation have been suggested as possible factors in plaque deposition in AD and DS (13,(18)(19)(20), a hypothesis that seems especially attractive in the case of DS individuals, in whom APP is known to be overexpressed (6). However, the data on the levels and splicing of APP in AD have been confusing; each group has studied a different set of brain regions and has used different techniques to measure APP levels and splicing.…”

mentioning

confidence: 87%

Expression of the amyloid precursor protein gene in mouse oocytes and embryos.

Fisher

Gearhart

Oster-Granite

1991

Proc. Natl. Acad. Sci. U.S.A.

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The amyloid precursor protein (APP) is thought to be processed aberrantly to yield the major constituent of the amyloid plaques observed in the brains of patients with Alzheimer disease and Down syndrome. However, the gene encoding APP is expressed widely in normal human tissues and in adult and fetal mouse tissues and is alternately spliced in a tissue-specific pattern in the adult. There is evidence that APP may function as a growth factor and as a mediator of cell adhesion and in these roles could be important in morphogenesis. As a step toward determining the role of APP in development and in determining how the adult pattern of tissuespecific splicing is established, we have used reverse transcription and the polymerase chain reaction to demonstrate APP expression in mouse oocytes, preimplantation embryos, and postimplantation embryonic stages to the late embryonic period. All three splicing forms described in mouse were present at each stage, although there were changes in the ratios of the splicing forms at different stages. Screens for APP clones in embryonic cDNA libraries from the egg cylinder stage and the early somite stage were used to confirm the results of the polymerase chain reaction, and APP clone abundance was found to increase 10-fold between these two stages./3-Amyloid peptide is the main component of the neuritic and cerebrovascular amyloid plaques of patients with Alzheimer disease (AD) (1) and aging individuals with Down syndrome (DS) (2). Its 42-amino acid sequence is found as part of a 695-amino acid protein, the amyloid precursor protein (APP695) (3-6). APP is encoded by a gene mapped on human chromosome 21 and in the syntenic region of mouse chromosome 16 (7, 8). The /3-amyloid peptide includes portions of both the extracellular domain and the single membranespanning domain of APP, but it is not known how the full-length protein is processed to yield the short peptide. However, it must involve a change in the normal processing of the protein, since the full-length precursor is cleaved constitutively at a site within the /3-amyloid sequence (9). Two other forms of APP have been described, APP751 and APP770, which are identical to APP695 except for the inclusion of either one or two additional exons, respectively, in the mRNA (10)(11)(12). Inclusion of only the second of these exons results in another form, APP714, detected in several human tissues but at much lower levels than the first three forms (13). A fifth form, APP563, has been cloned from a human brain cDNA library; its deduced sequence is identical to APP751 for the first 543 amino acids and then diverges for the remaining 20 amino acids (14). APP563, a minor component of the total APP message in brain, lacks the membrane-spanning domain and presumably encodes a secreted protein. Total APP expression is highest in the brain (6); APP695 is expressed predominantly in neurons (15), whereas APP751 and APP770 have been detected in every adult tissue examined (6). In the mouse, only splicing forms corresponding to APP695, AP...

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“…Wainer), which had been established by fusion of mouse neuroblastoma cell line N18TG2 and mouse septal neurons from postnatal 21-day-old C57BL/6 mouse, was used as a parent cholinergic cell line (Lee et al 1990). SN49 was transfected with either a pXT2 expression vector, which constructed by insertion of Pst I-Hind III fragment from pUC 18 into a EcoT22I-Hind III digested pXT1 vector (Stratagene, La Jolla, CA, USA), alone or a pXT2 vector inserting mouse APP695 cDNA (10.5Kb; Yamada et al 1987) by calcium phosphate coprecipitation method (Araki et al 1994). Eight lines which stably overexpress APP were obtained after 4 weeks of G418 selection.…”

Section: Methodsmentioning

confidence: 99%

The Decrement of Muscarinic Receptor-Mediated Calcium Influx by Overexpression of APP in a Mouse Cholinergic Cell Line.

Kunishita¹,

Ikeda²,

Araki³

et al. 1994

Tohoku J. Exp. Med.

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The effects of f3-amyloid precursor protein (APP) overexpressing on cell metabolisms of cholinergic neuronal hybridoma cell line (SN49) were examined. The cells stably overexpressing APP contained higher amount of GTP binding protein Go and cytosolic inactive protein kinase Ce, and showed less Ca2+ influx through muscarinic acetylcholine receptor ml compared to original and mock cells which had been transfected with a vector alone. The contents of sn-1, 2-diacylglycerol and cycilc AMP were also reduced in the APP transfectants, although the similar changes were observed in the mock cells. These findings strongly suggest that the overexpression of APP affect the transient receptor-mediated ion channel and calcium-related cell metabolisms in neuronal cells.APP overexpression; cholinergic cell line; muscarinic receptor; protein kinase C; GTP binding protein Deposition of f3-amyloid protein (fAP), which is composed of 39-42 of amino acids, in the brain was one of the major pathological hall-marks in Alzheimer's disease and aged Down's syndrome. fAP is generated by the cleavage of its precursor protein (APP 695, 751 and 770), 100-140 KDa integral mambrane proteins produced by three of alternative spliced mRNA from a gene on human chromosome 21. Proteolytic cleavage between residues 595 and 596 of APP695 forms amyloidogenic C-terminal fragments containing /3AP , while it between residue 612 and 163 produces non-amyloidogenic C-terminal fragments containing P3 (Haass et al. 1993). At least three of APP fragments are normally released to extra-cellular space by either so called c -or f3-secretary pathway. That is, secreted APPS (sAPP) and P3 are processed by a-pathway

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Complementary DNA for the mouse homolog of the human amyloid beta protein precursor

Cited by 141 publications

References 9 publications

Human and rodent Alzheimer β‐amyloid peptides acquire distinct conformations in membrane‐mimicking solvents

Human and rodent Alzheimer β‐amyloid peptides acquire distinct conformations in membrane‐mimicking solvents

Expression of the amyloid precursor protein gene in mouse oocytes and embryos.

The Decrement of Muscarinic Receptor-Mediated Calcium Influx by Overexpression of APP in a Mouse Cholinergic Cell Line.

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