Phenotypes Associated with This Genotype

Genotype
MGI:2679422

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

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

mortality/aging

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)

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)

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 )

• however, airway branching is not impaired

• marker analysis indicates impaired proximal and distal epithelial cell differentiation

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

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)