Phenotypes associated with this allele

• Allele Symbol: Atic^{tm1c(EUCOMM)Hmgu}
• Allele Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
• Allele ID: MGI:7510093
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Apoe^tm1Unc/Apoe^tm1Unc Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7511828
cn2	Apoe^tm1Unc/Apoe^tm1Unc Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu X/Tg(Myh11-icre/ERT2)1Soff	involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * C57BL/6N * FVB/N	MGI:7511826
cn3	Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:7511822
cn4	Atic^tm1c(EUCOMM)Hmgu/Atic^tm1c(EUCOMM)Hmgu X/Tg(Myh11-icre/ERT2)1Soff	involves: 129S4/SvJaeSor * C57BL/6J * C57BL/6N * FVB/N	MGI:7511824

Genotype
MGI:7511828

cn1

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

decreased susceptibility to atherosclerosis ( J:338121 )

• both sexes of tamoxifen-treated mice fed a Western diet for 12 weeks show a significant decrease in atherosclerotic lesion size in whole aortas as well as smaller lesion areas and less lipid deposition in the aortic sinuses than control mice

• ACTA2 staining of aortic sinuses showed a significant reduction in the vascular smooth muscle cell (VSMC) content of atherosclerotic lesions in both sexes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:338121 )

N • both male and female mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show no significant differences in plasma glucose levels relative to controls

decreased circulating cholesterol level ( J:338121 )

♂ • male, but not female, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks show a modest reduction in plasma cholesterol levels relative to controls

increased circulating triglyceride level ( J:338121 )

♀ • female, but not male, mice treated with tamoxifen and subsequently fed a Western diet for 12 weeks exhibit a significant increase in plasma triglyceride levels relative to controls

Genotype
MGI:7511826

cn2

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; X/Tg(Myh11-icre/ERT2)1Soff
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6J * C57BL/6N * FVB/N

cardiovascular system

decreased susceptibility to atherosclerosis ( J:338121 )

• tamoxifen-treated mice fed a Western diet for 12 weeks show a significant decrease in atherosclerotic lesion size in whole aortas as well as smaller lesion areas and less lipid deposition in the aortic sinuses than similarly-fed control mice

• ACTA2 staining showed a significant reduction in the vascular smooth muscle cell (VSMC) content of atherosclerotic lesions in the aortic sinus

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:338121 )

N • tamoxifen-treated mice fed a Western diet for 12 weeks show no significant differences in the level of plasma cholesterol, triglycerides, or glucose relative to controls

Genotype
MGI:7511822

cn3

• Allelic Composition: Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

cardiovascular system

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

abnormal vascular wound healing ( J:338121 )

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:338121 )

N • tamoxifen-treated mice fed a high-fat diet (HFD) for 12 weeks show no significant differences in HFD-induced body weight gain, fat content, leanness of body mass or fasting blood glucose levels relative to control mice, with no improvement in glucose clearance and insulin sensitivity

abnormal vascular wound healing ( J:338121 )

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a dramatic reduction in the neointima area and neointima/medial area ratio in sections 200 to 1200 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated common carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

cellular

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

abnormal cell cycle ( J:338121 )

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

muscle

decreased vascular smooth muscle cell proliferation ( J:338121 )

• in vitro, isolated mouse aortic smooth muscle cells (MASMCs) treated with 4-hydroxytamoxifen show a significant reduction in cell proliferation relative to wild-type cells, as determined by EdU staining

• flow cytometry analysis of cell cycle progression in 4-hydroxytamoxifen-treated MASMCs revealed an accumulation of cell populations in S phase, indicating S phase arrest in vascular smooth muscle cells

• 28 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury along with upregulation of VSMC differentiation markers MYH11 (SMMHC), CNN1 (calponin 1), ACTA2 and TAGLN (SM22alpha), implying that ATIC is required to promote a differentiated-to-proliferative phenotypic switch of VSMCs in vivo

Genotype
MGI:7511824

cn4

• Allelic Composition: Atic^{tm1c(EUCOMM)Hmgu}/Atic^{tm1c(EUCOMM)Hmgu}; X/Tg(Myh11-icre/ERT2)1Soff
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6J * C57BL/6N * FVB/N

cardiovascular system

decreased vascular smooth muscle cell proliferation ( J:338121 )

• 21 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury

abnormal vascular wound healing ( J:338121 )

• 21 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the neointima area and neointima/medial area ratio in sections 200 to 600 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

cellular

decreased vascular smooth muscle cell proliferation ( J:338121 )

• 21 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury

homeostasis/metabolism

abnormal vascular wound healing ( J:338121 )

• 21 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the neointima area and neointima/medial area ratio in sections 200 to 600 um from the site of ligation relative to control mice

• however, the external elastic lamina circumference of ligated carotid artery is similar to that in control mice, indicating that vascular constrictive remodeling is unaffected

muscle

decreased vascular smooth muscle cell proliferation ( J:338121 )

• 21 days after left common carotid artery ligation, tamoxifen-treated mice show a significant reduction in the % of proliferating (EdU+) VSMCs in cross-sections of arterial neointima relative to control mice

• expression of the proliferative marker PCNA is significantly reduced in ligated arteries 7 days after injury