Tg(APOA1)1Rub Transgene Detail MGI Mouse (MGI:3052540)

Tg(APOA1)1Rub
Transgene Detail

Nomenclature

Symbol:	Tg(APOA1)1Rub
Name:	transgene insertion 1, Edward M Rubin
MGI ID:	MGI:3052540
Synonyms:	apoA-I/A-IKO, hA-I, Hu apo AI
Transgene:	Tg(APOA1)1Rub Location: unknown

Transgene
origin

Strain of Origin:

C57BL/6

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene contains the human apolipoprotein A-I gene including the promoter. (J:42425)

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	tg4	tg5	tg6	tg7
cardiovascular system		√	√			√	√
decreased susceptibility to atherosclerosis		√	√			√
increased susceptibility to atherosclerosis							√
		tg1	tg2	tg3	tg4	tg5	tg6	tg7
cellular		√		√	√
increased cholesterol efflux		√		√	√
		tg1	tg2	tg3	tg4	tg5	tg6	tg7
homeostasis/metabolism		√	√	√	√	√	√	√
homeostasis/metabolism phenotype			N				N
increased cholesterol efflux		√		√	√
abnormal lipid homeostasis		√				√
abnormal lipid level		√
increased circulating cholesterol level		√		√	√		√	√
increased circulating HDL cholesterol level		√		√	√		√	√
increased circulating LDL cholesterol level							√
increased circulating VLDL cholesterol level							√
decreased circulating triglyceride level			√
increased circulating triglyceride level				√	√
decreased circulating cholesterol level					√
decreased circulating HDL cholesterol level					√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(APOA1)1Rub/Tg(APOA1)1Rub	C57BL/6-Tg(APOA1)1Rub/J
homeostasis/metabolism increased cholesterol efflux (J:107390) in macrophages in vitro abnormal lipid homeostasis (J:92450, J:129704) HDL particle size has a bimodal distribution with two peaks at 8.5 and 10.5 nm compared to the single peak at 9.9 nm for non-transgenic controls (J:92450) 90% of HDL particles contain human apoA-I instead of endogenous murine apo-AI (J:129704) HDL particle size has a bimodal distribution with two peaks similar to human HDL particles that contain apoA-I (J:129704) abnormal lipid level (J:42425) total APOA1 (mouse and human ) is increased two fold mouse APOA1 is reduced 95% mouse APOA2 is reduced 45% HDL particles include two subsets of larger (10.2-10.8nm) and smaller particles (8.4-8.6nm) as compared to control; these sizes fall with the range for human HDL-2b and HDL-3a, respectively increased circulating cholesterol level (J:42425) HDL cholesterol is increased two fold increased circulating HDL cholesterol level (J:42425) cardiovascular system decreased susceptibility to atherosclerosis (J:99552, J:107390, J:129704) reduced susceptibility to diet-induced fatty streak lesions (J:99552) macrophages transplanted into Apoa1^tm1Unc homozygotes or bone marrow transplanted into Apoa1^tm1Unc homozygotes in conjunction with Apoe^tm1Unc bone marrow confers resistance to diet-induced atherosclerosis (J:107390) there is a greater than 40-fold reduction in the mean lesion area found in the aorta of mice fed an atherogenic diet for 36 weeks compared to wild-type mice (J:129704) cellular increased cholesterol efflux (J:107390) in macrophages in vitro
Genotype	Allelic Composition	Genetic Background
tg2	Tg(APOA1)1Rub/0	involves: C57BL/6
homeostasis/metabolism homeostasis/metabolism phenotype (J:128254) despite being fed an atherogenic diet, mice exhibit no change in total cholesterol, triglyceride and HDL-cholesterol levels compared to similarly treated wild-type mice decreased circulating triglyceride level (J:121992) cardiovascular system decreased susceptibility to atherosclerosis (J:128254) atherosclerotic lesions are 3-fold smaller than in Tg(APOA1)1Rub Tg(AlbLCAT)1Jdm or Tg(APOA1)1Rub Tg(CETP)5203Tall mice and 4-fold smaller than in Tg(AlbLCAT)1Jdm mice the risk of developing atherosclerotic lesions greater than 50th percentile is 4.3-fold lower than in wild-type mice
Genotype	Allelic Composition	Genetic Background
tg3	Apoa1^tm1Unc/Apoa1^tm1Unc Tg(APOA1)1Rub/0	involves: 129P2/OlaHsd * C57BL/6
homeostasis/metabolism increased cholesterol efflux (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub increased circulating cholesterol level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub increased circulating HDL cholesterol level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub increased circulating triglyceride level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub cellular increased cholesterol efflux (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub
Genotype	Allelic Composition	Genetic Background
tg4	Tg(APOA1)1Rub/0 Tg(APOA2)3Rub/0	involves: C57BL/6
cellular increased cholesterol efflux (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub homeostasis/metabolism increased cholesterol efflux (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub decreased circulating cholesterol level (J:121992) decreased circulating HDL cholesterol level (J:121992) increased circulating cholesterol level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub increased circulating HDL cholesterol level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub increased circulating triglyceride level (J:129136) compared to in Apoa1^tm1Unc homozygotes with or without Tg(APOA2)3Rub
Genotype	Allelic Composition	Genetic Background
tg5	Tg(APOA1)1Rub/? Tg(APOA2)3Rub/?	involves: C57BL/6
homeostasis/metabolism abnormal lipid homeostasis (J:92450, J:129704) HDL particle size has a broad size distribution between 8 and 9.5 nm but is missing the 10.5 nm particles observed in mice carrying just the Tg(APOA1)1Rub transgene (J:92450) HDL particle size has a broad size distribution similar to human HDL particles that contain apoA-I and apoA-II (J:129704) cardiovascular system decreased susceptibility to atherosclerosis (J:129704) there is a 2.7-fold reduction in the mean lesion area found in the aorta of mice fed an atherogenic diet for 36 weeks compared to wild-type mice
Genotype	Allelic Composition	Genetic Background
tg6	Tg(AlbLCAT)1Jdm/0 Tg(APOA1)1Rub/0	involves: C57BL/6 * FVB/N
homeostasis/metabolism homeostasis/metabolism phenotype (J:128254) despite being fed an atherogenic diet, mice exhibit no change in total cholesterol, triglyceride and HDL-cholesterol levels compared to similarly treated wild-type mice increased circulating cholesterol level (J:121992) up to 4.2-fold compared to in Tg(APOA1)1Rub mice increased circulating HDL cholesterol level (J:121992) 2-fold compared to in Tg(AlbLCAT)1Jdm or Tg(APOA1)1Rub mice increased circulating LDL cholesterol level (J:121992) increased circulating VLDL cholesterol level (J:121992) cardiovascular system increased susceptibility to atherosclerosis (J:128254) atherosclerotic lesions are 3-fold larger than in Tg(APOA1)1Rub mice
Genotype	Allelic Composition	Genetic Background
tg7	Tg(AlbLCAT)1Jdm/0 Tg(APOA1)1Rub/0 Tg(APOA2)3Rub/0	involves: C57BL/6 * FVB/N
homeostasis/metabolism increased circulating cholesterol level (J:121992) 2-fold compared to in Tg(APOA1)1Rub Tg(APOA2)3Rub mice increased circulating HDL cholesterol level (J:121992) 2-fold compared to in Tg(AlbLCAT)1Jdm or Tg(APOA1)1Rub Tg(APOA2)3Rub mice

Notes

Transgenic mice display a two fold increase in total plasma cholesterol levels and greater than a four fold decrease in the levels of mouse APOA1. Two lines were produced, A2 and A16.

References

Original:	J:42425 Rubin EM et al., "Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses." Proc Natl Acad Sci U S A 1991 Jan 15;88(2):434-8
All:	20 reference(s)

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