Tg(Prnp-Abca1)EHol Transgene Detail MGI Mouse (MGI:3800823)

Tg(Prnp-Abca1)EHol
Transgene Detail

Nomenclature

Symbol:	Tg(Prnp-Abca1)EHol
Name:	transgene insertion E, David M Holtzman
MGI ID:	MGI:3800823
Synonyms:	PrP-mAbca1 line E
Transgene:	Tg(Prnp-Abca1)EHol Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x CBA)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	A transgenic construct containing the mouse Abca1 (ATP-binding cassette, sub-family A (ABC1), member 1) gene under the control of the mouse Prnp (prion protein) promoter was injected into fertilized B6CBAF1 eggs. Founder line E was subsequently established. These founder line E mice have a 6-fold increase in expression of ABCA1 in the cortex over wildtype levels. Transgene expression is high in total brain tissue, kidney, testis and muscle as detected by Western blot analysis. (J:131400)

Find Mice (IMSR)

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

Carrying this Mutation:

Mouse Strains: 1 strain 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	tg3
endocrine/exocrine glands		√
abnormal testis morphology		√
seminiferous tubule degeneration		√
abnormal testis development		√
decreased testis weight		√
testicular atrophy		√
		tg1	tg2	tg3
homeostasis/metabolism		√
homeostasis/metabolism phenotype		N
abnormal protein level		√
		tg1	tg2	tg3
nervous system		√	√	√
amyloid beta deposits		√	√	√
abnormal glial cell physiology		√
		tg1	tg2	tg3
other phenotype		√	√	√
amyloid beta deposits		√	√	√
		tg1	tg2	tg3
reproductive system		√
abnormal testis morphology		√
seminiferous tubule degeneration		√
abnormal testis development		√
decreased testis weight		√
testicular atrophy		√
abnormal spermatogenesis		√
male infertility		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(Prnp-Abca1)EHol/0	involves: C57BL/6 * CBA
reproductive system abnormal testis morphology (J:131400) 3-fold increased numbers of apoptotic cells in testes relative to controls seminiferous tubule degeneration (J:131400) tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei abnormal testis development (J:131400) testes exhibit maturation arrest due to absence of mature products of spermatogenesis decreased testis weight (J:131400) 50% reduction in testes mass relative to wild-type controls testicular atrophy (J:131400) severe atrophy abnormal spermatogenesis (J:131400) elongated spermatids and spermatozoa are absent in testes of mutant males male infertility (J:131400) nervous system amyloid beta deposits (J:131400) in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus almost no deposits are observed in hilus of dentate gyrus of hippocampus thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months thioflavin-S positive plaques are associated with reactive microglia abnormal glial cell physiology (J:131400) Apoe-containing lipoprotein particles secreted by astrocytes contain more lipid than those secreted by non-transgenic controls; lipoprotein fractions contain a greater ratio of cholesterol to Apoe other phenotype amyloid beta deposits (J:131400) in 12-month old mice have frequent amyloid beta (Abeta) deposits in cortex and hippocampus including molecular layer of hippocampus almost no deposits are observed in hilus of dentate gyrus of hippocampus thioflavin-S positive fibrillar Abeta plaques are frequently observed in cortex and hippocampus at 12 months thioflavin-S positive plaques are associated with reactive microglia endocrine/exocrine glands abnormal testis morphology (J:131400) 3-fold increased numbers of apoptotic cells in testes relative to controls seminiferous tubule degeneration (J:131400) tubules display atrophy with marked degenerative changes such as large increase in multinucleated giant cells and cells with condensed nuclei abnormal testis development (J:131400) testes exhibit maturation arrest due to absence of mature products of spermatogenesis decreased testis weight (J:131400) 50% reduction in testes mass relative to wild-type controls testicular atrophy (J:131400) severe atrophy homeostasis/metabolism homeostasis/metabolism phenotype (J:131400) plasma levels of cholesterol including HDL-associated cholesterol and phospolipids, and Apoe are not significantly different from controls at 3 months abnormal protein level (J:131400) mice show 40% reduction in Apoe levels in hippocampus at 3 months; in CSF, levels of Apoe are decreased >40% brain lysates contain significantly lower levels of Clusterin than control samples
Genotype	Allelic Composition	Genetic Background
tg2	Apoe^tm1Unc/Apoe^tm1Unc Tg(Prnp-Abca1)EHol/0	involves: 129P2/OlaHsd * C57BL/6 * CBA
nervous system amyloid beta deposits (J:131400) frequent deposits are observed in hilus of dentate gyrus mice show 2- to 3-fold less Abeta in the brain relative to Tg(APPV717F)109Ili, Apoe-wild-type controls almost no thioflavin-S positive fibrillar Abeta plaques are observed in cortex and hippocampus other phenotype amyloid beta deposits (J:131400) frequent deposits are observed in hilus of dentate gyrus mice show 2- to 3-fold less Abeta in the brain relative to Tg(APPV717F)109Ili, Apoe-wild-type controls almost no thioflavin-S positive fibrillar Abeta plaques are observed in cortex and hippocampus
Genotype	Allelic Composition	Genetic Background
tg3	Tg(APPV717F)109Ili/0 Tg(Prnp-Abca1)EHol/0	involves: C57BL/6 * CBA
nervous system amyloid beta deposits (J:131400) at 12 months, rare amyloid beta (Abeta) deposits are observed in the cortex, with occasional deposits in the molecular layer of hippocampus and frequent Abeta deposits in the hilus of the dentate gyrus; mice show 3-fold less Abeta in the brain relative to Tg(APPV717F)109Ili, Abca1-wild-type controls fibrillar Abeta plaques are frequently observed in cortex and hippocampus Abeta deposits are almost all diffuse, with little true amyloid very few clusters of reactive microglia are seen in brain other phenotype amyloid beta deposits (J:131400) at 12 months, rare amyloid beta (Abeta) deposits are observed in the cortex, with occasional deposits in the molecular layer of hippocampus and frequent Abeta deposits in the hilus of the dentate gyrus; mice show 3-fold less Abeta in the brain relative to Tg(APPV717F)109Ili, Abca1-wild-type controls fibrillar Abeta plaques are frequently observed in cortex and hippocampus Abeta deposits are almost all diffuse, with little true amyloid very few clusters of reactive microglia are seen in brain

References

Original:	J:131400 Wahrle SE et al., "Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease." J Clin Invest 2008 Feb;118(2):671-82
All:	1 reference(s)

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