Phenotypes associated with this allele

• Allele Symbol: Dll4^tm1Frad
• Allele Name: targeted mutation 1, Freddy Radtke
• Allele ID: MGI:3828266
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Dll4^tm1Frad/Dll4^tm1Frad Foxn1^tm3(cre)Nrm/Foxn1^+	B6.Cg-Dll4^tm1Frad Foxn1^tm3(cre)Nrm	MGI:3828268
cn2	Dll4^tm1Frad/Dll4^tm1Frad Tg(Mx1-cre)1Cgn/0	B6.Cg-Dll4^tm1Frad Tg(Mx1-cre)1Cgn	MGI:3828267
cn3	Dll4^tm1Frad/Dll4^+ Isl1^tm1(cre)Tmj/Isl1^+	involves: 129S1/Sv * 129X1/SvJ	MGI:7545577

Genotype
MGI:3828268

cn1

• Allelic Composition: Dll4^tm1Frad/Dll4^tm1Frad; Foxn1^tm3(cre)Nrm/Foxn1⁺
• Genetic Background: B6.Cg-Dll4^tm1Frad Foxn1^tm3(cre)Nrm

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

immune system

abnormal thymus cell ratio ( J:143472 )

• absolute numbers of double negative cells in the thymus is increased 2-fold compared to in Dll4^tm1Frad homozygous control mice

• only CD4+CD25- DN1 cells are present and these DN cells are B220+ unlike in control mice

• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in control mice

decreased thymocyte number ( J:143472 )

• thymi exhibit a 14-fold reduction in the number of thymocytes compared to in Dll4^tm1Frad homozygous control mice

increased immature B cell number ( J:143472 )

• the absolute numbers of immature B cells in the thymus are increased 340-fold compared to in Dll4^tm1Frad homozygous control mice

abnormal T cell differentiation ( J:143472 )

• T cells differentiated in the thymus is nearly completely blocked unlike in Dll4^tm1Frad homozygous control mice

decreased double-positive T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of double positive T cells in the thymus

decreased CD4-positive, alpha-beta T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of CD4+ T cells in the thymus

• absolute numbers of CD4+ T cells is reduced 180- to 3000-fold compared to Dll4^tm1Frad homozygous in control mice

decreased CD8-positive, alpha-beta T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of CD8+ T cells in the thymus

• absolute numbers of CD8+ T cells is reduced 180- to 3000-fold compared to in Dll4^tm1Frad homozygous control mice

hematopoietic system

abnormal thymus cell ratio ( J:143472 )

• absolute numbers of double negative cells in the thymus is increased 2-fold compared to in Dll4^tm1Frad homozygous control mice

• only CD4+CD25- DN1 cells are present and these DN cells are B220+ unlike in control mice

• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in control mice

decreased thymocyte number ( J:143472 )

• thymi exhibit a 14-fold reduction in the number of thymocytes compared to in Dll4^tm1Frad homozygous control mice

increased immature B cell number ( J:143472 )

• the absolute numbers of immature B cells in the thymus are increased 340-fold compared to in Dll4^tm1Frad homozygous control mice

abnormal T cell differentiation ( J:143472 )

• T cells differentiated in the thymus is nearly completely blocked unlike in Dll4^tm1Frad homozygous control mice

decreased double-positive T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of double positive T cells in the thymus

decreased CD4-positive, alpha-beta T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of CD4+ T cells in the thymus

• absolute numbers of CD4+ T cells is reduced 180- to 3000-fold compared to Dll4^tm1Frad homozygous in control mice

decreased CD8-positive, alpha-beta T cell number ( J:143472 )

• flow cytometry indicates a near complete loss of CD8+ T cells in the thymus

• absolute numbers of CD8+ T cells is reduced 180- to 3000-fold compared to in Dll4^tm1Frad homozygous control mice

endocrine/exocrine glands

abnormal thymus cell ratio ( J:143472 )

• absolute numbers of double negative cells in the thymus is increased 2-fold compared to in Dll4^tm1Frad homozygous control mice

• only CD4+CD25- DN1 cells are present and these DN cells are B220+ unlike in control mice

• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in control mice

decreased thymocyte number ( J:143472 )

• thymi exhibit a 14-fold reduction in the number of thymocytes compared to in Dll4^tm1Frad homozygous control mice

Genotype
MGI:3828267

cn2

• Allelic Composition: Dll4^tm1Frad/Dll4^tm1Frad; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Dll4^tm1Frad Tg(Mx1-cre)1Cgn

immune system

immune system phenotype ( J:143472 )

N • when bone marrow is transplanted into CD45.1+ wild-type hosts reconstitution is normal

Genotype
MGI:7545577

cn3

• Allelic Composition: Dll4^tm1Frad/Dll4⁺; Isl1^tm1(cre)Tmj/Isl1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cardiovascular system

abnormal cardiac outflow tract development ( J:308916 )

• 9 of 28 embryos show outflow tract alignment defects

• however, septation of the outflow tract is preserved

double outlet right ventricle ( J:308916 )

• in embryos with a severe ventricular septal defect

overriding aortic valve ( J:308916 )

• in embryos with a shallower ventricular septal defect

ventricular septal defect ( J:308916 )

• some embryos show a prominent ventricular septal defect while in others this is more shallow

abnormal pulmonary valve morphology ( J:308916 )

• pulmonary valve arises more cranially and exits the right ventricle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Adams-Oliver syndrome		DOID:0060227	OMIM:100300 OMIM:614219 OMIM:614814 OMIM:615297 OMIM:616028 OMIM:PS100300	J:308916