Phenotypes associated with this allele

• Allele Symbol: Ets1^tm2Jml
• Allele Name: targeted mutation 2, Jeffrey M Leiden
• Allele ID: MGI:2182780
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ets1^tm2Jml/Ets1^tm2Jml	involves: 129X1/SvJ * C57BL/6	MGI:3608775
hm2	Ets1^tm2Jml/Ets1^tm2Jml	involves: 129X1/SvJ * C57BL/6J	MGI:7541419
ht3	Ets1^tm2Jml/Ets1^+	involves: 129X1/SvJ * C57BL/6J	MGI:7541420
cn4	Ets1^tm2Jml/Ets1^tm2Jml Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Pax3^tm1(cre)Joe/Pax3^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * C57BL/6NCrl	MGI:7541421

Genotype
MGI:3608775

hm1

• Allelic Composition: Ets1^tm2Jml/Ets1^tm2Jml
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:50627 )

postnatal lethality, incomplete penetrance ( J:50627 )

• approximately 50% of homozygotes survive until 4 weeks of age

hematopoietic system

hematopoietic system phenotype ( J:50627 )

N • normal numbers of splenic IgM⁺ B220⁺ B cells

N • splenocytes have normal expression of IL2RB, IL2RG, IL15RA and IL18

increased plasma cell number ( J:50627 )

• increased numbers of splenic and lymph node plasma cells with serum IgM levels elevated by approximately 5 fold

decreased NK cell number ( J:50627 )

• reduced NK cell numbers evidenced by diminished splenic DX5⁺ CD3^- cells and diminished splenic NK1.1⁺ CD3^- cells

• lymph nodes and bone marrow do not contain detectable DX5⁺ CD3^- cells

decreased T cell number ( J:50627 )

• slightly reduced numbers of splenic T cells, particularly CD8⁺ T cells

decreased thymocyte number ( J:50627 )

• 4 to 8 week old homozygotes have approximately 65% reduction in thymocyte numbers with low levels of CD4 expressed on many CD8+ thymocytes

abnormal CD8-positive, alpha beta T cell morphology ( J:50627 )

abnormal leukocyte physiology ( J:50627 )

abnormal NK cell physiology ( J:50627 )

• poly (I:C) stimulated splenocytes produce reduced amounts of IFNG and IL12

impaired natural killer cell mediated cytotoxicity ( J:50627 )

• splenocytes fail to lyse YAC-1 tumor cells, B2m^-/- lyphoid blasts, and MHC class I deficient RMA-S tumor cells are not rejected at a normal rate in vivo

• addition of IL12, IL2 and IL15 fails to restore YAC-1 cytolysis

abnormal T cell activation ( J:50627 )

decreased T cell proliferation ( J:50627 )

• splenic T cells display a defect in activation following cross-linking of the T cell receptor

immune system

increased plasma cell number ( J:50627 )

• increased numbers of splenic and lymph node plasma cells with serum IgM levels elevated by approximately 5 fold

decreased NK cell number ( J:50627 )

• reduced NK cell numbers evidenced by diminished splenic DX5⁺ CD3^- cells and diminished splenic NK1.1⁺ CD3^- cells

• lymph nodes and bone marrow do not contain detectable DX5⁺ CD3^- cells

decreased T cell number ( J:50627 )

• slightly reduced numbers of splenic T cells, particularly CD8⁺ T cells

decreased thymocyte number ( J:50627 )

• 4 to 8 week old homozygotes have approximately 65% reduction in thymocyte numbers with low levels of CD4 expressed on many CD8+ thymocytes

abnormal CD8-positive, alpha beta T cell morphology ( J:50627 )

abnormal leukocyte physiology ( J:50627 )

abnormal NK cell physiology ( J:50627 )

• poly (I:C) stimulated splenocytes produce reduced amounts of IFNG and IL12

impaired natural killer cell mediated cytotoxicity ( J:50627 )

• splenocytes fail to lyse YAC-1 tumor cells, B2m^-/- lyphoid blasts, and MHC class I deficient RMA-S tumor cells are not rejected at a normal rate in vivo

• addition of IL12, IL2 and IL15 fails to restore YAC-1 cytolysis

abnormal T cell activation ( J:50627 )

decreased T cell proliferation ( J:50627 )

• splenic T cells display a defect in activation following cross-linking of the T cell receptor

endocrine/exocrine glands

decreased thymocyte number ( J:50627 )

• 4 to 8 week old homozygotes have approximately 65% reduction in thymocyte numbers with low levels of CD4 expressed on many CD8+ thymocytes

cellular

decreased T cell proliferation ( J:50627 )

• splenic T cells display a defect in activation following cross-linking of the T cell receptor

Genotype
MGI:7541419

hm2

• Allelic Composition: Ets1^tm2Jml/Ets1^tm2Jml
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

cardiovascular system

decreased cardiac neural crest cell number ( J:334073 )

• at E14.5, LacZ staining showed a decreased number of cardiac neural crest cells at the aortic valve

abnormal cardiac outflow tract development ( J:334073 )

• septation of the proximal outflow tract (OFT) is impaired

double outlet right ventricle ( J:334073 )

• at E15.5, three of 4 hearts show DORV phenotypes by MRI analysis

• at E14.5, all (4 of 4) hearts show DORV by serial section analysis through the outflow tracts (OFTs)

overriding aortic valve ( J:334073 )

• at E15.5, one of 4 hearts exhibit an overriding aorta phenotype by MRI analysis

bicuspid aortic valve ( J:334073 )

• at E14.5, three of 4 hearts exhibit a bi-leaflet (bisinuate) aortic valve

abnormal heart right ventricle outflow tract morphology ( J:334073 )

• by E18.5, the infundibular sleeve consisting of cardiac myocytes is severely reduced; instead of the tendon of the infundibulum, a fibrous outlet septum produces continuity between leaflets of the aortic and pulmonary valves in a side-by-side orientation

embryo

decreased cardiac neural crest cell number ( J:334073 )

• at E14.5, LacZ staining showed a decreased number of cardiac neural crest cells at the aortic valve

nervous system

decreased cardiac neural crest cell number ( J:334073 )

• at E14.5, LacZ staining showed a decreased number of cardiac neural crest cells at the aortic valve

Genotype
MGI:7541420

ht3

• Allelic Composition: Ets1^tm2Jml/Ets1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

integument

belly spot ( J:334073 )

• mice exhibit a patch of white fur on their abdomen

pigmentation

belly spot ( J:334073 )

• mice exhibit a patch of white fur on their abdomen

Genotype
MGI:7541421

cn4

• Allelic Composition: Ets1^tm2Jml/Ets1^tm2Jml; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Pax3^tm1(cre)Joe/Pax3⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J * C57BL/6NCrl

cardiovascular system

abnormal cardiac outflow tract development ( J:334073 )

abnormal conotruncal ridge morphology ( J:334073 )

• at E13.5, alpha-actinin staining showed that cardiac myocytes are separated from the tdTomato positive cNCCs in the OFT cushion

• by E15.5, far fewer cardiomyocytes are in contact with tdTomato positive cNCCs in the OFT cushion, indicating impaired muscularization

double outlet right ventricle ( J:334073 )

• by E15.5, cNCCs persist as a fibrous outlet septum in the setting of DORV

embryo

abnormal neural crest cell physiology ( J:334073 )

• 12.7% of explanted cultured cardiac neural crest cells (cNCCs) make cell-cell contacts versus 8.5% of control cNCCs; strikingly, 81% of those contacts fail to separate within 2 h versus only 31.2% in control cNCCs, suggesting increased cell-cell adhesion

abnormal cardiac neural crest cell migration ( J:334073 )

• at E9.5, fewer tdTomato-labeled cNCCs are detected in the developing outflow tract (OFT) relative to control embryos, suggesting a delay in cNCC migration

• at E10.5, a nearly complete absence of tdTomato cNCCs is seen in the proximal component of the OFT cushions

• lack of tdTomato cNCCs in the proximal outflow cushion is less severe at E11.5; abundant cNCCs are found in the distal and intermediate outflow cushions, but not in proximal cushions, consistent with delayed migration

• moreover, number of Pax3Cre-tdTomato expressing cells that co-express SOX10 is markedly decreased and the linear migration pattern from the neural tube toward the heart is disrupted; most of tdTomato positive-expressing cells lacking SOX10 expression are located rather peripherally

• N-cadherin staining showed upregulation of N-cadherin expression in migratory NCCs at E8.5 and E9.5

• time-lapse image analysis of explanted cultured cNCCs showed a significant decrease in migration velocity relative to controls

cellular

abnormal neural crest cell physiology ( J:334073 )

• 12.7% of explanted cultured cardiac neural crest cells (cNCCs) make cell-cell contacts versus 8.5% of control cNCCs; strikingly, 81% of those contacts fail to separate within 2 h versus only 31.2% in control cNCCs, suggesting increased cell-cell adhesion

abnormal cardiac neural crest cell migration ( J:334073 )

• at E9.5, fewer tdTomato-labeled cNCCs are detected in the developing outflow tract (OFT) relative to control embryos, suggesting a delay in cNCC migration

• at E10.5, a nearly complete absence of tdTomato cNCCs is seen in the proximal component of the OFT cushions

• lack of tdTomato cNCCs in the proximal outflow cushion is less severe at E11.5; abundant cNCCs are found in the distal and intermediate outflow cushions, but not in proximal cushions, consistent with delayed migration

• moreover, number of Pax3Cre-tdTomato expressing cells that co-express SOX10 is markedly decreased and the linear migration pattern from the neural tube toward the heart is disrupted; most of tdTomato positive-expressing cells lacking SOX10 expression are located rather peripherally

• N-cadherin staining showed upregulation of N-cadherin expression in migratory NCCs at E8.5 and E9.5

• time-lapse image analysis of explanted cultured cNCCs showed a significant decrease in migration velocity relative to controls