Tg(H2-K-AKR1B1)1Tj Transgene Detail MGI Mouse (MGI:3703741)

Tg(H2-K-AKR1B1)1Tj
Transgene Detail

Nomenclature

Symbol:	Tg(H2-K-AKR1B1)1Tj
Name:	transgene insertion 1, University of Tokushima School of Medicine
MGI ID:	MGI:3703741
Synonyms:	hAR-Tg
Transgene:	Tg(H2-K-AKR1B1)1Tj Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x DBA/2)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	Expression of the full length human aldose reductase (AKR1B1) cDNA is under control of the murine H2-K^d promoter. Northern and Wester blotting shows expression of human aldose reductase mRNA and protein in all tissues tested. (J:120049)

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
cardiovascular system		√	√	√
abnormal blood vessel morphology		√
increased susceptibility to atherosclerosis			√	√
		tg1	tg2	tg3
homeostasis/metabolism		√	√	√
abnormal glucose homeostasis		√
hyperglycemia			√	√
abnormal enzyme/coenzyme activity		√
abnormal circulating cholesterol level			√
		tg1	tg2	tg3
immune system			√
abnormal macrophage physiology			√
		tg1	tg2	tg3
renal/urinary system		√
abnormal renal glomerular capsule		√
		tg1	tg2	tg3
vision/eye		√
cataracts		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(H2-K-AKR1B1)1Tj/0	involves: C57BL/6 * DBA/2
vision/eye cataracts (J:120049) 7/15 transgenic mice developed cataracts when fed a 20% galactose diet for 7 days; 2/7 only displayed cataracts while 5 mice also developed occlusion of the retinochoroidal vessels renal/urinary system abnormal renal glomerular capsule (J:120049) multiple fibrinous deposits were observed in the Bowman's capsule of many glomeruli in 4/5 mice fed a normal diet mice fed a 20% galactose diet show fibrinous deposits in Bowman's capsules of kidneys while littermates fed the same diet show no histopathological changes cardiovascular system abnormal blood vessel morphology (J:120049) 5/15 mice fed a 20% galactose diet for 7 days developed cataracts and occlusion of retinochoroidal vessels while another 2 mice developed vascular occlusion only homeostasis/metabolism abnormal glucose homeostasis (J:120049) sorbitol concentration in liver, kidney, and muscle after intake of 30% glucose chow for 5 days increases by 1.7, 2.1, and 2.0, respectively compared to control littermates; levels with normal diet are not significantly different between transgenic mice and controls abnormal enzyme/coenzyme activity (J:120049) activity of purified AR from transgenic mouse muscle is 5-6 fold higher than in muscle from littermates
Genotype	Allelic Composition	Genetic Background
tg2	Ldlr^tm1Her/Ldlr^tm1Her Tg(H2-K-AKR1B1)1Tj/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
homeostasis/metabolism hyperglycemia (J:100916) streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet these high glucose levels persist for at least 12 weeks after STZ treatment abnormal circulating cholesterol level (J:100916) streptozotocin (STZ) induced diabetes in mice fed a high fat diet leads to blood cholesterol levels that are twice those of non-diabetic mice 6 weeks post-induction blood cholesterol levels increase to three times greater than in non-diabetic mice 8 weeks after STZ treatment cardiovascular system increased susceptibility to atherosclerosis (J:100916) non-diabetic mice fed a high fat diet have a total lesion area of 10.7% in their aortas compared to 8.0% in Ldlr^tm1Her homozyogotes that do not carry the transgene diabetic mice fed a high fat diet for 6 weeks have a total aortic lesion area of 37.5% compared to 23.4% lesion area in diabetic Ldlr^tm1Her homozyogotes that do not carry the transgene these differences in aortic lesion area between transgenic and non-transgenic Ldlr^tm1Her homozyogotes increase the longer the mice are on a high fat diet the greatest differences are observed in the aortic arch of diabetic mice where there is a 65% increase in the lesion area 6 weeks after disease induction compared to Ldlr^tm1Her homozyogotes that do not carry the transgene immune system abnormal macrophage physiology (J:100916) peritoneal macrophages have a higher uptake of acetylated LDL compared macrophages from Ldlr^tm1Her homozyogotes that do not carry the transgene mean uptake of acetylated-LDL is 5.27 micrograms/mg cellular protein vs 1.18 micrograms/mg cellular protein in controls
Genotype	Allelic Composition	Genetic Background
tg3	Ldlr^tm1Her/Ldlr⁺ Tg(H2-K-AKR1B1)1Tj/0	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2
homeostasis/metabolism hyperglycemia (J:100916) streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet these high glucose levels persist for at least 12 weeks after STZ treatment cardiovascular system increased susceptibility to atherosclerosis (J:100916) in mice made diabetic by STZ treatment and fed a cholesterol/cholic acid containing diet for 12 weeks, total aortic lesion area is doubled compared to Ldlr^tm1Her heterozygotes that do not carry the transgene the presence of the transgene causes no difference in lesion size in non-diabetic mice

References

Original:	J:120049 Yamaoka T et al., "Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA." Diabetologia 1995 Mar;38(3):255-61
All:	4 reference(s)

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