Tg(Prnp-ITM2B/APP695*42)A12Emcg Transgene Detail MGI Mouse (MGI:3710689)

Tg(Prnp-ITM2B/APP695*42)A12Emcg
Transgene Detail

Nomenclature

Symbol:	Tg(Prnp-ITM2B/APP695*42)A12Emcg
Name:	transgene insertion A12, Eileen McGowan
MGI ID:	MGI:3710689
Synonyms:	BRI-Abeta1-42, BRI-Abeta42A, BRI-Abeta42A line 12e, RI-Abeta42A (12e)
Transgene:	Tg(Prnp-ITM2B/APP695*42)A12Emcg Location: unknown

Transgene
origin

Strain of Origin:

(C3H x C57BL/6)F1 X C57BL/6

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene was generated with a mouse prion promoter upstream of a BRI-Abeta42 fusion construct, containing a cDNA sequence from human type 2 transmembrane protein (BRI or ITM2B) fused in-frame with a "wildtype APP695" cDNA sequence encoding amyloid-beta42 (Abeta42) at the furin-like cleavage site; the C-terminal 23 amino acid ABri peptide of BRI was replaced with the Abeta42 sequence. Mice from the founder with the highest Abeta42 plasma levels, line BRI-Abeta42A (12e) were donated to the Jackson Laboratory. Transgenic fusion protein expression approximates levels of endogenous mouse APP expression and is expressed in patterns characteristic of the Prnp promoter, with highest expression in cerebellar granule cells and hippocampus. Full length Abeta fusion protein is most highly expressed with processed Abeta42 peptide expressed at lower levels (J:101023, J:120781)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 2 strains available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1	tg2
nervous system		√	√
abnormal forebrain morphology		√	√
gliosis		√
amyloid beta deposits		√	√
abnormal hindbrain morphology			√
		tg1	tg2
other phenotype		√	√
amyloidosis		√	√
amyloid beta deposits		√	√

		tg1	tg2
Disease Models		√
Alzheimer Disease; AD		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(Prnp-ITM2B/APP695*42)A12Emcg/0

involves: C3H * C57BL/6

nervous systemabnormal forebrain morphology (J:101023)

forebrain pathology only consistently develops after 12 months of age

gliosis (J:101023)

reactive gliosis is associated with plaques

amyloid beta deposits (J:101023)

cored plaques can be observed as early as 3 months in molecular layer of cerebella of transgenic mice and becoming more pronounced with age; occasional extracellular plaques are seen in the entorhinal/piriform cortices and hippocampus at 6 months of age, but aren't consistently found until >12 months of age

oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb

extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques

compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months

endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice

tau pathology is not evident

other phenotypeamyloidosis (J:101023)

Abeta1-42 peptide levels in 3-month old transgenic brains are ~1- to 1.5-fold higher than levels in 3- and 6-month oldTg(APPSWE)2576Kahs controls

amyloid beta deposits (J:101023)

oldest mice show widespread pathology with cored and diffuse plaques in cerebellum, cortex, hippocampus, and olfactory bulb

extracellular amyloid plaques show dense amyloid cores with radiating fibrils; many bundles of dystrophic neurites are observed at the periphery of these plaques

compact plaques range from 38 um in diameter at 3 months to 58 um at 1-18 months

endogenous mouse Abeta is detected in some cored plaques and in diffuse deposits in older mice

tau pathology is not evident

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD		J:101023

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

tg2

Tg(APPSWE)2576Kha/0
Tg(Prnp-ITM2B/APP695*42)A12Emcg/0

involves: C3H * C57BL/6 * SJL

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD OMIM ID: 104300		tg1	Tg(Prnp-ITM2B/APP695*42)A12Emcg/0	involves: C3H * C57BL/6	J:101023

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

References

Original:	J:101023 McGowan E et al., "Abeta42 is essential for parenchymal and vascular amyloid deposition in mice." Neuron 2005 Jul 21;47(2):191-9
All:	4 reference(s)

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