Phenotypes associated with this allele

• Allele Symbol: Egr1^tm1Jmi
• Allele Name: targeted mutation 1, Jeffrey Milbrandt
• Allele ID: MGI:2384433
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Egr1^tm1Jmi/Egr1^tm1Jmi	B6.129-Egr1^tm1Jmi	MGI:4821393
hm2	Egr1^tm1Jmi/Egr1^tm1Jmi	involves: 129	MGI:2658680
hm3	Egr1^tm1Jmi/Egr1^tm1Jmi	involves: 129 * C57BL/6	MGI:4821394
cx4	Egr1^tm1Jmi/Egr1^tm1Jmi Tg(Scgb1a1-rtTA,-tTS,tetO-TGFB1*)1Eli/?	involves: 129 * C57BL/6	MGI:4821398
cx5	Apoe^tm1Unc/Apoe^tm1Unc Egr1^tm1Jmi/Egr1^tm1Jmi	involves: 129 * C57BL/6	MGI:4821395
cx6	Egr1^tm1Jmi/Egr1^tm1Jmi Tg(TRAMP)8247Ng/?	involves: 129 * C57BL/6	MGI:4821397
cx7	Egr1^tm1Jmi/Egr1^tm1Jmi Tg(Defcr2-TAg)#Jig/?	involves: 129 * C57BL/6 * FVB/N	MGI:4821396

Genotype
MGI:4821393

hm1

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi
• Genetic Background: B6.129-Egr1^tm1Jmi

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

skeleton

increased osteoclast cell number ( J:51107 )

• elevated osteoclast formation regardless of estrogen levels

decreased bone mineral density ( J:62113 )

• decreased 10% by 4 months of age

abnormal trabecular bone morphology ( J:62113 )

• increased cancellous bone formation

cardiovascular system

cardiovascular system phenotype ( J:96665 )

N • no atherosclerotic lesions at the root of the aorta

liver/biliary system

liver/biliary system phenotype ( J:128421 )

N • galactoseamine/LPS induced liver injury is attenuated early

N • less evidence of apoptosis

N • very little hemorrhage

N • no evidence of necrosis

abnormal liver physiology ( J:128421 )

• survive 7 hours rather than 6 hours after galactoseamine/LPS treatment

• extensive liver hemorrhage and hepatocyte apoptosis by 7 hours

liver inflammation ( J:128421 )

• neutrophiles in parenchyma 50% lower than in controls

• reduced extravasation of neutrophiles in liver

homeostasis/metabolism

abnormal circulating tumor necrosis factor level ( J:128421 )

• early increases after treatment with galactoseamine/LPS are similar to controls

• increase is 65% less 4 hours after treatment

• increase is 75% less 5.5 hours after treatment

abnormal circulating alanine transaminase level ( J:128421 )

• 30% less increase in alanine aminotransferase levels in plasma after galactoseamine/LPS treatment than in controls

hematopoietic system

increased osteoclast cell number ( J:51107 )

• elevated osteoclast formation regardless of estrogen levels

immune system

increased osteoclast cell number ( J:51107 )

• elevated osteoclast formation regardless of estrogen levels

abnormal circulating tumor necrosis factor level ( J:128421 )

• increase is 75% less 5.5 hours after treatment

• early increases after treatment with galactoseamine/LPS are similar to controls

• increase is 65% less 4 hours after treatment

liver inflammation ( J:128421 )

• neutrophiles in parenchyma 50% lower than in controls

• reduced extravasation of neutrophiles in liver

Genotype
MGI:2658680

hm2

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi
• Genetic Background: involves: 129

endocrine/exocrine glands

abnormal ovary morphology ( J:35132 )

♀

absent corpus luteum ( J:35132 )

♀ • ovaries were similar in weight to wild-type

Leydig cell atrophy ( J:35132 )

♂ • atrophic Leydig cells; however, spermatogenesis is normal

homeostasis/metabolism

abnormal vascular wound healing ( J:61294 )

• less neointimal expansion seen 28 days after endothelial denudation of the femoral artery than in controls

abnormal circulating progesterone level ( J:35132 )

• serum levels of progesterone are reduced, however serum levels of estradiol are normal

decreased luteinizing hormone level ( J:35132 )

• LH undetected in females in the pituitary

• LH levels decreased in males in the pituitary

• LH levels did not increase after ovariectomy in the pituitary

reproductive system

abnormal ovary morphology ( J:35132 )

♀

absent corpus luteum ( J:35132 )

♀ • ovaries were similar in weight to wild-type

Leydig cell atrophy ( J:35132 )

♂ • atrophic Leydig cells; however, spermatogenesis is normal

decreased uterus weight ( J:35132 )

♀ • ~30% the weight of wild-type uterus

abnormal reproductive system physiology ( J:35132 )

abnormal ovulation ( J:35132 )

♀ • ovulation could be induced by exogenous gonadotropins

absent estrous cycle ( J:35132 )

♀ • females are anestrous

female infertility ( J:35132 )

♀

cardiovascular system

cardiac fibrosis ( J:61294 )

• fibrotic lesions in the heart regardless of treatment with adrenoreceptor agonists

• heart weight/body weight ratios are normal

abnormal vascular wound healing ( J:61294 )

• less neointimal expansion seen 28 days after endothelial denudation of the femoral artery than in controls

Genotype
MGI:4821394

hm3

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi
• Genetic Background: involves: 129 * C57BL/6

growth/size/body

postnatal growth retardation ( J:123870 )

• mild

increased spleen weight ( J:123870 )

• 15-20 fold increase in spleen weight

• expanded erythroid and myeloid cells in spleen

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

• mice with lymphomas do not develop myeloproliferative disease

liver/biliary system

liver/biliary system phenotype ( J:105638 )

N • ethanol feeding does not induce liver steatosis

increased liver triglyceride level ( J:105638 )

• slightly elevated liver triglycerides with ethanol feeding

abnormal liver size ( J:105638 )

• liver weight/body weight ratio does not increase with ethanol feeding as happens with controls

abnormal liver physiology ( J:105638 )

impaired liver regeneration ( J:93996 )

• hepatocellular proliferation after partial hepatectomy normal for first 36 hours

• proliferation is significantly reduced at 48 hours

cellular

abnormal mitosis ( J:93996 )

• mitosis impaired between metaphase and anaphase

decreased mitotic index ( J:93996 )

• lower frequency of mitosis in the liver 48 hours after hepatectomy

• frequency of mitosis in the liver remains more or less constant from 48 to 72 hours after hepatectomy

neoplasm

neoplasm ( J:123870 )

N • spontaneous tumors do not develop

increased T cell derived lymphoma incidence ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

• mice with lymphomas do not develop myeloproliferative disease

increased incidence of tumors by chemical induction ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

increased skin papilloma incidence ( J:99386 )

• skin tumors induced by treatment with DMBA and TPA appear to be papillomas

decreased tumor latency ( J:99386 )

• mice treated with the mutagen DMBA and tumor promoter TPA develop skin tumors around 8 weeks rather than 12.5 weeks as in controls

homeostasis/metabolism

abnormal homeostasis ( J:105638 )

abnormal circulating alanine transaminase level ( J:105638 )

• serum alanine aminotransferase is not increased by ethanol feeding whereas levels increase 2 fold in controls

increased liver triglyceride level ( J:105638 )

• slightly elevated liver triglycerides with ethanol feeding

abnormal tumor necrosis factor level ( J:105638 )

• TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

abnormal physiological response to xenobiotic ( J:105638 )

• liver weight/body weight ratio does not increase with ethanol feeding as happens with controls

• serum alanine aminotransferase is not increased by ethanol feeding whereas levels increase 2 fold in controls

• TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

• no effect of ethanol diet on LPS sensitivity

increased incidence of tumors by chemical induction ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

abnormal response to injury ( J:135238 )

decreased cerebral infarct size ( J:135238 )

• infarcts are much smaller in total area after temporary middle cerebral artery occlusion

• neurological deficits are mild

• less edema than in controls

delayed wound healing ( J:152898 )

• reduced rate of wound healing

• less collagen deposition

• fewer alpha smooth muscle cell positive myofibroblasts

hematopoietic system

increased T cell derived lymphoma incidence ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

• mice with lymphomas do not develop myeloproliferative disease

increased spleen weight ( J:123870 )

• 15-20 fold increase in spleen weight

• expanded erythroid and myeloid cells in spleen

abnormal erythropoiesis ( J:123870 )

• ineffective erythropoiesis in bone marrow and spleen

anemia ( J:123870 )

increased bone marrow cell number ( J:123870 )

thrombocytopenia ( J:123870 )

abnormal hematopoietic stem cell morphology ( J:149801 )

• two fold increase in hematopoietic stem cells in the S/G2-M phase of the cell cycle

• no buildup of stem cells in the bone marrow

• level of circulating hematopoietic stem cells is dramatically increased

abnormal leukocyte morphology ( J:123870 )

abnormal neutrophil morphology ( J:123870 )

• dysplastic neutrophils in bone marrow and spleen

abnormal leukocyte cell number ( J:123870 )

• mildly elevated

increased lymphocyte cell number ( J:123870 )

abnormal microglial cell physiology ( J:135238 )

• elevated numbers of activated microglial cells an macrophage but fewer than in controls

immune system

immune system phenotype ( J:105638 )

N • no effect of ethanol diet on LPS sensitivity

increased T cell derived lymphoma incidence ( J:123870 )

• ENU treatment at 4 and 20 weeks weeks results in T-cell lymphomas in 53% of mice compared to 26% of controls treated at 3 weeks and 10% of controls treated at 20 weeks

• mice with lymphomas do not develop myeloproliferative disease

increased spleen weight ( J:123870 )

• 15-20 fold increase in spleen weight

• expanded erythroid and myeloid cells in spleen

abnormal leukocyte morphology ( J:123870 )

abnormal neutrophil morphology ( J:123870 )

• dysplastic neutrophils in bone marrow and spleen

abnormal leukocyte cell number ( J:123870 )

• mildly elevated

increased lymphocyte cell number ( J:123870 )

abnormal microglial cell physiology ( J:135238 )

• elevated numbers of activated microglial cells an macrophage but fewer than in controls

abnormal tumor necrosis factor level ( J:105638 )

• TNF alpha levels remain constant with ethanol feeding whereas they increase 20 fold in controls

decreased inflammatory response ( J:152898 )

• lower inflammatory response to four daily subcutaneous bleomycin injections

• lower inflammatory response to a single subcutaneous TGF beta injection

respiratory system

respiratory system phenotype ( J:152898 )

N • bleomycin induced lung pathologies are attenuated

pulmonary fibrosis ( J:152898 )

• number and size of subpleural and interstitial fibrotic foci is reduced

• diminished collagen accumulation

pulmonary interstitial fibrosis ( J:152898 )

• reduced

vision/eye

abnormal eye morphology ( J:123287 )

abnormal cornea morphology ( J:123287 )

• smaller radius of curvature at 40 days of age than in controls

increased eye anterior chamber depth ( J:123287 )

• deeper anterior chamber of the eye at 56 days of age

abnormal eye size ( J:123287 )

• longer eyes (axial eye length) than controls at 42 days of age

abnormal vision ( J:123287 )

• reduced refraction relative to controls

nervous system

abnormal microglial cell physiology ( J:135238 )

• elevated numbers of activated microglial cells an macrophage but fewer than in controls

decreased cerebral infarct size ( J:135238 )

• infarcts are much smaller in total area after temporary middle cerebral artery occlusion

• neurological deficits are mild

• less edema than in controls

integument

thick dermal layer ( J:152898 )

• bleomycin induced dermal thickening more modest than in controls

• less sclerotic than controls

• less collagen accumulation

• reduced accumulation of alpha-smooth musclew actin myofibroblasts

increased skin papilloma incidence ( J:99386 )

• skin tumors induced by treatment with DMBA and TPA appear to be papillomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myelodysplastic syndrome		DOID:0050908	OMIM:614286	J:123870

Genotype
MGI:4821398

cx4

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi; Tg(Scgb1a1-rtTA,-tTS,tetO-TGFB1*)1Eli/?
• Genetic Background: involves: 129 * C57BL/6

respiratory system

respiratory system phenotype ( J:92469 )

N • early apoptosis is not observed

lung inflammation ( J:92469 )

• inflammation occurs but with moderately reduced inflammatory cell accumulation relative to controls carrying only the transgene

abnormal pulmonary alveolus morphology ( J:92469 )

• alveolar remodeling is diminished

pulmonary fibrosis ( J:92469 )

• fibrosis response is reduced

immune system

lung inflammation ( J:92469 )

• inflammation occurs but with moderately reduced inflammatory cell accumulation relative to controls carrying only the transgene

Genotype
MGI:4821395

cx5

• Allelic Composition: Apoe^tm1Unc/Apoe^tm1Unc; Egr1^tm1Jmi/Egr1^tm1Jmi
• Genetic Background: involves: 129 * C57BL/6

cardiovascular system

abnormal susceptibility to atherosclerosis ( J:96665 )

• 2.5 fold decrease in lesions at 14 weeks of age compared to Apoe^{tm1Unc/tmiUnc}

• 7 fold difference in lesion numbers at 24 weeks of age

Genotype
MGI:4821397

cx6

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi; Tg(TRAMP)8247Ng/?
• Genetic Background: involves: 129 * C57BL/6

neoplasm

increased tumor latency ( J:67125 )

♂ • significantly delayed prostate tumor formation

♂ • fewer "PIN" lesions at 20 weeks than controls but not significantly

Genotype
MGI:4821396

cx7

• Allelic Composition: Egr1^tm1Jmi/Egr1^tm1Jmi; Tg(Defcr2-TAg)#Jig/?
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

endocrine/exocrine glands

decreased prostate gland tumor incidence ( J:67125 )

• rate of prostatic intra-epithelial neoplasia formation is similar to controls

• significantly fewer foci of invasive carcinomas at both 25 and 35 weeks

• tumors smaller than in controls

mortality/aging

premature death ( J:67125 )

• mortality due to prostate cancer

• survival time about 46.5 weeks as compared to 35-36 weeks for controls

neoplasm

decreased tumor incidence ( J:67125 )

• 70% are free of tumors at 35 weeks of age

decreased prostate gland tumor incidence ( J:67125 )

• rate of prostatic intra-epithelial neoplasia formation is similar to controls

• significantly fewer foci of invasive carcinomas at both 25 and 35 weeks

• tumors smaller than in controls

cardiovascular system

decreased angiogenesis ( J:67125 )

• less angiogenesis at 25 weeks of age

• lower microvascular density

cellular

cellular phenotype ( J:67125 )

N • cellular proliferation rate equivalent to controls

reproductive system

decreased prostate gland tumor incidence ( J:67125 )

• rate of prostatic intra-epithelial neoplasia formation is similar to controls

• significantly fewer foci of invasive carcinomas at both 25 and 35 weeks

• tumors smaller than in controls