Phenotypes associated with this allele

• Allele Symbol: Ep300⁺
• Allele Name: wild type
• Allele ID: MGI:2435653
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ep300^tm1Dli/Ep300^+	either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)	MGI:3512271
ht2	Ep300^tm1Reck/Ep300^+	involves: 129P2/OlaHsd	MGI:2679422
ht3	Ep300^tm1Pkb/Ep300^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3578232
ht4	Ep300^tm1Dli/Ep300^+	involves: 129S4/SvJae * C57BL/6	MGI:3512285
cn5	Cd19^tm1(cre)Cgn/Cd19^+ Ep300^tm2Reck/Ep300^+	involves: 129/Sv * 129P2/OlaHsd * C57BL/6	MGI:3843174
cn6	Cd19^tm1(cre)Cgn/Cd19^+ Ep300^tm2Reck/Ep300^+	involves: 129/Sv * 129P2/OlaHsd * FVB/N	MGI:3843175
cx7	Ep300^tm1Pkb/Ep300^+ Myb^tm1Ssp/Myb^+	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6	MGI:3578233
cx8	Crebbp^tm2Pkb/Crebbp^+ Ep300^tm3Pkb/Ep300^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3626197
cx9	Ep300^Plt6/Ep300^+ Mpl^tm1Wsa/Mpl^tm1Wsa	involves: 129S1/Sv * C57BL/6	MGI:3813262
cx10	Crebbp^tm1Dli/Crebbp^+ Ep300^tm1Dli/Ep300^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:3512279
cx11	Ep300^tm3Pkb/Ep300^+ Tg(IghMyc)22Bri/0	involves: 129S6/SvEvTac * C57BL/6	MGI:3626202
cx12	Ep300^tm3Pkb/Ep300^+ Tg(IghMyc)22Bri/0	involves: 129S6/SvEvTac * C57BL * SJL	MGI:3626201

Genotype
MGI:3512271

ht1

• Allelic Composition: Ep300^tm1Dli/Ep300⁺
• Genetic Background: either: 129S4/SvJae or (involves: 129S4/SvJae * C57BL/6)

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

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:47301 )

• a fraction of heterozygotes die as early as at E10.5

• at weaning, 55% fewer heterozygotes are obtained on a 129/Sv inbred genetic background

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

embryo

decreased embryo size ( J:47301 )

• at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos

open neural tube ( J:47301 )

• a fraction of heterozygotes exhibit defective neural tube closure

• in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

growth/size/body

decreased embryo size ( J:47301 )

• at E10.5, heterozygotes with exencephaly are consistently smaller than wild-type embryos

nervous system

open neural tube ( J:47301 )

• a fraction of heterozygotes exhibit defective neural tube closure

• in heterozygotes, the neural tube defect is restricted to the anterior part of the hindbrain and the midbrain; the rest of the neural tube fuses normally

• Background Sensitivity: considerably less lethality is observed on a mixed 129 x C57BL/6 background and none on an incipient congenic C57BL/6 background

exencephaly ( J:47301 )

• at E10.5, 6% of 129/Sv C57BL/6 and 19% of 129/Sv heterozygous mutant embryos display exencephaly

• the neural lumen (ventricle) is collapsed; abnormal masses of neural tissue are also observed

Genotype
MGI:2679422

ht2

• Allelic Composition: Ep300^tm1Reck/Ep300⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

perinatal lethality, complete penetrance ( J:85949 , J:85950 )

• embryos developing to term are either born dead or become cyanotic within minutes after birth due to respiratory failure (J:85949)

lethality throughout fetal growth and development, incomplete penetrance ( J:85949 , J:85950 )

• more than 1/3 (42/70) of embryos die between E12.5 and E15.5 (J:85949)

• most die between E12.5 and E16.5 due to heart failure or perinatally due to inability to breathe (J:85950)

embryonic lethality during organogenesis, incomplete penetrance ( J:85949 , J:85950 )

• more than 1/3 (42/70) of embryos die between E12.5 and E15.5 (J:85949)

• most die between E12.5 and E16.5 due to heart failure or perinatally due to inability to breathe (J:85950)

growth/size/body

decreased body size ( J:85949 )

• most mutants are 20% smaller in size than wild-type

respiratory system

abnormal lung development ( J:85949 )

• most lungs are developmentally arrested around the early saccular stage since air saccules fail to form

• marker analysis indicates impaired proximal and distal epithelial cell differentiation

• however, airway branching is not impaired

respiratory failure ( J:85949 )

• neonatal lungs fail to inflate

cardiovascular system

abnormal vasculogenesis ( J:85949 )

• a delay or reduction in the development of the coronary vessel network is apparent by E13.5

myocardium hypoplasia ( J:85949 )

• reduction in muscle mass of heart

• retardation of myocardium development

thin ventricle myocardium compact layer ( J:85949 )

• about 80% of embryos show a reduction in myocardial compact layer thickness of both ventricular chambers

thin myocardium ( J:85949 )

• reduction in thickness of the myocardium is first visible at E11 and is primarily in the ventricular but not atrial wall

abnormal heart development ( J:85949 )

• more severe than in Crebbp^tm1Reck heterozygotes

abnormal epicardium development ( J:85949 )

• epicardium formation is not complete at E11 but the epicardium is formed around most hearts by E12.5

delayed heart development ( J:85949 )

• mutants exhibit a delay in heart development

atrial septal defect ( J:85949 )

• three embryos have an atrial septum closure defect (ASD)

abnormal atrioventricular septum morphology ( J:85949 )

• atrial septum closure defect (ASD) is associated with an underdeveloped atrioventricular septum

ventricular septal defect ( J:85949 )

• ventricular septum closure defect (VSD) is seen in 7/8 mutants at E14.5 and in 5/6 mutants at E15.5, however by E16.5 most mutants have a closed ventricular septum, indicating a 2-3 day delay in closure

perimembraneous ventricular septal defect ( J:85949 )

• mutants with little myocardial thinning also have underdeveloped leaflets and a VSD, however this is restricted to the membranous part located at the tip of the septum

abnormal heart valve morphology ( J:85949 )

• VSD is accompanied by underdeveloped or malformed valve leaflets

thin ventricular wall ( J:85949 )

• some hearts show a thin ventricular wall prior to the onset of vascularization

hemorrhage ( J:85949 )

• edema is often accompanied by peripheral hemorrhage, however by E16.5 and E18.5, mutants no longer exhibit edema and hemorrhage

internal hemorrhage ( J:85949 )

• about 1/3 of embryos at E13.5 exhibit blood leakage around ventricles

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:85949 )

• the thickness of the epithelial cell layer of the midgut is greatly expanded

abnormal small intestine morphology ( J:85949 )

• mutants exhibit increased mesenchymal cell proliferation in the small intestine at E18.5

abnormal small intestinal villus morphology ( J:85949 )

• delay in villi formation by 2-4 days in the small intestine, showing no mesenchymal invagination at E14.5 and E16.5

muscle

abnormal muscle morphology ( J:85950 )

• mutants exhibit a reduction in the size of muscle by E14.5

• reduction in muscle size is not due to decreased proliferation, increased apoptosis or impaired migration of muscle precursors into the limb buds

myocardium hypoplasia ( J:85949 )

• reduction in muscle mass of heart

• retardation of myocardium development

thin ventricle myocardium compact layer ( J:85949 )

• about 80% of embryos show a reduction in myocardial compact layer thickness of both ventricular chambers

thin myocardium ( J:85949 )

• reduction in thickness of the myocardium is first visible at E11 and is primarily in the ventricular but not atrial wall

abnormal myogenesis ( J:85950 )

• marker analysis indicates impaired muscle formation

abnormal muscle fiber morphology ( J:85950 )

• interfibrillar space of muscle fibers at E18.5 is increased

• muscle fibers appear loose and disorganized at E18.5

decreased skeletal muscle fiber size ( J:85950 )

• muscle fiber size is reduced at E14.5 and E18.5 in trapezius, tongue, diaphragm, and intercostal muscles

homeostasis/metabolism

cyanosis ( J:85949 )

• neonates become cyanotic within minutes following birth

edema ( J:85949 , J:85950 )

• edema is seen in all mutants at E14.5 and E15.5, however most embryos aged E16.5 to E18.5 no longer exhibit edema (J:85949)

• all mutants at E14.5 exhibit peripheral edema (J:85950)

Genotype
MGI:3578232

ht3

• Allelic Composition: Ep300^tm1Pkb/Ep300⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

thrombocytosis ( J:98329 )

• slight increase in platelets but otherwise normal

Genotype
MGI:3512285

ht4

• Allelic Composition: Ep300^tm1Dli/Ep300⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

neoplasm

neoplasm ( J:60630 )

N • at 10-21 months, heterozygotes show no increased incidence of hematologic malignancies compared with wild-type mice

hematopoietic system

hematopoietic system phenotype ( J:60630 )

N • at 12-18 months, heterozygotes exhibit neither splenomegaly nor hematopoietic differentiation defects

Genotype
MGI:3843174

cn5

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Ep300^tm2Reck/Ep300⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:147840 )

• all mice die by prematurely, but female mice exhibit a shorter life span than male mice (median survival of 29 weeks for females compared with 43 weeks for males)

• Background Sensitivity: mice have a shorter life span than mice on a mixed background containing C57BL/6

immune system

arteritis ( J:147840 )

• mice exhibit paravascular cell infiltration and thickening of the artery walls unlike in wild-type mice

enlarged spleen ( J:147840 )

increased spleen weight ( J:147840 )

• at 4 to 6 months

abnormal B cell differentiation ( J:147840 )

• mature B cells in aged mice lack CD23 expression unlike in wild-type mice indicating an age-dependent loss of part of the normal B cell differentiation program

abnormal transitional stage B cell morphology ( J:147840 )

• fewer transitional B cells with the AA4.1+ phenotype are detected compared to in wild-type mice

• however, the number of total transitional B cells is normal

decreased marginal zone B cell number ( J:147840 )

increased B cell number ( J:147840 )

• the number of activated B cells in the spleen is more than in wild-type mice

increased activated T cell number ( J:147840 )

• in the spleen

abnormal spleen marginal zone macrophage morphology ( J:147840 )

• decreased in number

intermingled spleen red and white pulp ( J:147840 )

enlarged lymph nodes ( J:147840 )

• in some mice

abnormal adaptive immunity ( J:147840 )

• following ovalbumin immunization, the memory response upon boosting with ovalbumin is 3-fold less than in similarly treated wild-type mice

increased B cell apoptosis ( J:147840 )

• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice

• however, mature B cells exhibit normal apoptosis rates

decreased B cell proliferation ( J:147840 )

• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice

• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4

abnormal humoral immune response ( J:147840 )

• prior to ovalbumin immunization, mice exhibit 3-fold more ovalbumin-specific immunoglobins compared to in wild-type mice

• however, the humoral response 14 days after immunization is normal

increased immunoglobulin level ( J:147840 )

• 1.6-fold at 10 months of age

increased IgG2b level ( J:147840 )

• 3.7-fold

increased susceptibility to systemic lupus erythematosus ( J:147840 )

• Background Sensitivity: mice develop systemic lupus erythematosus symptoms earlier in life than when mice are on a mixed background containing FVB/N

increased anti-double stranded DNA antibody level ( J:147840 )

kidney inflammation ( J:147840 )

• interstitial

glomerulonephritis ( J:147840 )

renal/urinary system

kidney inflammation ( J:147840 )

• interstitial

glomerulonephritis ( J:147840 )

abnormal renal glomerulus morphology ( J:147840 )

• glomeruli are enlarged and often filled with homogeneous protein deposits in the kidney, spleen, liver, and lungs unlike in wild-type mice

renal glomerular protein deposits ( J:147840 )

renal fibrosis ( J:147840 )

cardiovascular system

arteritis ( J:147840 )

• mice exhibit paravascular cell infiltration and thickening of the artery walls unlike in wild-type mice

hematopoietic system

increased B cell apoptosis ( J:147840 )

• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice

• however, mature B cells exhibit normal apoptosis rates

decreased B cell proliferation ( J:147840 )

• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice

• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4

enlarged spleen ( J:147840 )

increased spleen weight ( J:147840 )

• at 4 to 6 months

abnormal B cell differentiation ( J:147840 )

• mature B cells in aged mice lack CD23 expression unlike in wild-type mice indicating an age-dependent loss of part of the normal B cell differentiation program

abnormal transitional stage B cell morphology ( J:147840 )

• fewer transitional B cells with the AA4.1+ phenotype are detected compared to in wild-type mice

• however, the number of total transitional B cells is normal

extramedullary hematopoiesis ( J:147840 )

• with islands of granulopoiesis

increased megakaryocyte cell number ( J:147840 )

• 4- to 20-fold in the spleen

decreased marginal zone B cell number ( J:147840 )

increased B cell number ( J:147840 )

• the number of activated B cells in the spleen is more than in wild-type mice

increased activated T cell number ( J:147840 )

• in the spleen

abnormal spleen marginal zone macrophage morphology ( J:147840 )

• decreased in number

intermingled spleen red and white pulp ( J:147840 )

increased immunoglobulin level ( J:147840 )

• 1.6-fold at 10 months of age

increased IgG2b level ( J:147840 )

• 3.7-fold

cellular

increased B cell apoptosis ( J:147840 )

• following IgM stimulation, apoptosis of transitional B cells is greater than in wild-type mice

• however, mature B cells exhibit normal apoptosis rates

decreased B cell proliferation ( J:147840 )

• in response to BCR engagement by anti-IgM, B cell proliferation is less than in wild-type mice

• however, B cells exhibit normal proliferation in response to LPS, IL4, anti-CD40 and ODN1668, and IgM proliferation can be restored by co-stimulation with anto-CD40 or IL4

growth/size/body

enlarged spleen ( J:147840 )

increased spleen weight ( J:147840 )

• at 4 to 6 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:147840

Genotype
MGI:3843175

cn6

• Allelic Composition: Cd19^tm1(cre)Cgn/Cd19⁺; Ep300^tm2Reck/Ep300⁺
• Genetic Background: involves: 129/Sv * 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:147840 )

• Background Sensitivity: mice have a longer life span than mice on a mixed background containing C57BL/6

• all mice die prematurely, but female mice exhibit a shorter life span than male mice (median survival of 73 weeks for females compared with over 90 weeks for males)

immune system

increased susceptibility to systemic lupus erythematosus ( J:147840 )

• Background Sensitivity: mice develop systemic lupus erythematosus symptoms later in life than when mice are on a mixed background containing C57BL/6

Genotype
MGI:3578233

cx7

• Allelic Composition: Ep300^tm1Pkb/Ep300⁺; Myb^tm1Ssp/Myb⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6

hematopoietic system

decreased thymocyte number ( J:98329 )

• 40% reduction in numbers

abnormal megakaryocyte morphology ( J:98329 )

• megakaryocyte ploidy reduced relative to controls

thrombocytosis ( J:98329 )

• large increase in platelet numbers seen at 2-3 weeks of age but not at 5-6 weeks

immune system

decreased thymocyte number ( J:98329 )

• 40% reduction in numbers

endocrine/exocrine glands

decreased thymocyte number ( J:98329 )

• 40% reduction in numbers

Genotype
MGI:3626197

cx8

• Allelic Composition: Crebbp^tm2Pkb/Crebbp⁺; Ep300^tm3Pkb/Ep300⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

growth/size/body

decreased body size ( J:103607 )

• compound mutants are smaller than littermates

craniofacial

abnormal craniofacial morphology ( J:103607 )

• some compound heterozygotes have craniofacial defects

Genotype
MGI:3813262

cx9

• Allelic Composition: Ep300^Plt6/Ep300⁺; Mpl^tm1Wsa/Mpl^tm1Wsa
• Genetic Background: involves: 129S1/Sv * C57BL/6

immune system

increased eosinophil cell number ( J:140200 )

• the eosinophil number is almost double that of Mpl^tm1Wsa homozygotes and is similar to wild-type mice

hematopoietic system

increased megakaryocyte cell number ( J:140200 )

• megakaryocyte numbers in the bone marrow and spleen are more than double what is found of wild-type mice

abnormal megakaryocyte progenitor cell morphology ( J:140200 )

• clonogenic myeloid progenitor cells are also significantly elevated by more than 3-fold in the spleen

increased eosinophil cell number ( J:140200 )

• the eosinophil number is almost double that of Mpl^tm1Wsa homozygotes and is similar to wild-type mice

abnormal platelet morphology ( J:140200 )

• platelet count is increased more than 2-fold compared to Mpl^tm1Wsa homozygotes but is about half the number found in wild-type mice

Genotype
MGI:3512279

cx10

• Allelic Composition: Crebbp^tm1Dli/Crebbp⁺; Ep300^tm1Dli/Ep300⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

mortality/aging

prenatal lethality, complete penetrance ( J:47301 )

• unexpectedly, compound heterozygotes die in utero

embryo

decreased embryo size ( J:47301 )

• compound heterozygotes are smaller than control embryos

open neural tube ( J:47301 )

• compound heterozygotes exhibit a severe open neural tube defect similar to that observed in Ep300^tm1Dli or Crebbp^tm1Dli homozygous mutants

growth/size/body

decreased embryo size ( J:47301 )

• compound heterozygotes are smaller than control embryos

nervous system

open neural tube ( J:47301 )

• compound heterozygotes exhibit a severe open neural tube defect similar to that observed in Ep300^tm1Dli or Crebbp^tm1Dli homozygous mutants

exencephaly ( J:47301 )

• compound heterozygotes exhibit extensive exencephaly

Genotype
MGI:3626202

cx11

• Allelic Composition: Ep300^tm3Pkb/Ep300⁺; Tg(IghMyc)22Bri/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

neoplasm

abnormal tumor incidence ( J:103607 )

• on a C57BL/6 background, surivival of transgenic mutants carrying the mutant Ep300 allele were identical to that of Ep300-sufficient transgenic mice

Genotype
MGI:3626201

cx12

• Allelic Composition: Ep300^tm3Pkb/Ep300⁺; Tg(IghMyc)22Bri/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL * SJL

neoplasm

abnormal tumor susceptibility ( J:103607 )

• on a hybrid background presence of a single Ep300^tm3Pkb allele decreased the median survival time by about 8-10 weeks compared to wild-type transgenic littermates