Phenotypes associated with this allele

• Allele Symbol: Tbx5^tm1.1Jse
• Allele Name: targeted mutation 1.1, Jonathan G Seidman
• Allele ID: MGI:2387851
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx5^tm1.1Jse/Tbx5^tm1.1Jse	either: (involves: 129/SvEv) or (involves: Black Swiss)	MGI:3052528
ht2	Tbx5^tm1.1Jse/Tbx5^+	either: (involves: 129/Sv) or (involves: Black Swiss)	MGI:3052529
ht3	Tbx5^tm1.1Jse/Tbx5^+	involves: 129/Sv * Black Swiss	MGI:3623769
ht4	Tbx5^tm1.1Jse/Tbx5^+	involves: Black Swiss	MGI:3617912
cx5	Sall4^Gt(XE027)Byg/Sall4^+ Tbx5^tm1.1Jse/Tbx5^+	involves: 129P2/OlaHsd * Black Swiss * C57BL/6	MGI:3617911

Genotype
MGI:3052528

hm1

• Allelic Composition: Tbx5^tm1.1Jse/Tbx5^tm1.1Jse
• Genetic Background: either: (involves: 129/SvEv) or (involves: Black Swiss)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:71845 , J:112887 )

• do not survive past day E10.5 (J:71845)

cardiovascular system

abnormal heart morphology ( J:112887 )

• E9.5 hearts have a single columnar ventricle projecting from the chest cavity and posterior structures (atria and left ventricle) are severely hypoplastic

abnormal heart development ( J:71845 )

• impaired cardiac differentiation

absent atrioventricular cushions ( J:71845 )

• AV cushion formation was not initiated

failure of heart looping ( J:71845 )

• cardiac looping did not occur

abnormal heart tube morphology ( J:71845 )

• deformed linear heart tube was observed with a hypoplastic posterior heart segment and continued growth of anterior segments

• sinoatrial structures (i.e., primitive atria and inflow tract) and the primitive LV were severely hypoplastic in these embryos

common atrium ( J:71845 )

• only a single small atrium is seen at E9.5

embryo

embryonic growth arrest ( J:71845 )

• development seems to be arrested at E9.5

Genotype
MGI:3052529

ht2

• Allelic Composition: Tbx5^tm1.1Jse/Tbx5⁺
• Genetic Background: either: (involves: 129/Sv) or (involves: Black Swiss)

mortality/aging

perinatal lethality, incomplete penetrance ( J:112887 )

• Background Sensitivity: greater than 90% perinatal death in the 129S/SvEv background and 59% in a Black Swiss background

cardiovascular system

abnormal impulse conducting system morphology ( J:92050 )

abnormal atrioventricular bundle morphology ( J:92050 )

• atrioventricular bundle remains immature in adults

abnormal left posterior bundle morphology ( J:92050 )

• the left ventricular bundle branch remain immature in adults

abnormal right bundle morphology ( J:92050 )

• right ventricular bundle branching defects of varying severity are seen

atrial septal defect ( J:112887 )

• all exhibit atrial septal defects; atrial septal defects are larger than in Tbx5^tm1Jse heterozygotes

• however, do not have ventricular septal defects

dilated heart atrium ( J:112887 )

• all show an enlargement of the atria

abnormal cardiovascular system physiology ( J:112887 )

• cardiac monitoring over 48 hours shows sporadic electrophysiological anomalies, including occurrences of ventricular tachycardia, sinus rhythm with atrial complexes, secondary degree AV block and sinoatrial pauses

abnormal sinus arrhythmia ( J:112887 )

• occurrences of sinus rhythm anomalies with atrial complexes

ventricular tachycardia ( J:112887 )

• occurrences of ventricular tachycardia

abnormal impulse conducting system conduction ( J:92050 )

• conduction time from sinoatrial node to atrioventricular node did not decrease with age as was seen for controls

• AH interval is significantly longer in adults

abnormal atrioventricular node conduction ( J:92050 )

• defective conduction through atrioventricular node

atrioventricular block ( J:112887 )

prolonged PQ interval ( J:92050 , J:112887 )

• PQ interval is significantly longer in adults but not newborns (J:92050)

• increase in PQ-interval duration at 12 weeks of age, indicative of first degree atrioventricular block; block is more severe than that seen in Tbx5^tm1Jse heterozygotes (J:112887)

prolonged QRS complex duration ( J:92050 )

• QRS interval elongation in both newborns and adults (depolarization and activation of ventricular myocardium)

abnormal sinoatrial node conduction ( J:112887 )

• sinoatrial pauses

muscle

abnormal impulse conducting system morphology ( J:92050 )

abnormal atrioventricular bundle morphology ( J:92050 )

• atrioventricular bundle remains immature in adults

abnormal left posterior bundle morphology ( J:92050 )

• the left ventricular bundle branch remain immature in adults

abnormal right bundle morphology ( J:92050 )

• right ventricular bundle branching defects of varying severity are seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Holt-Oram syndrome		DOID:0060468	OMIM:142900	J:92050 , J:112887

Genotype
MGI:3623769

ht3

• Allelic Composition: Tbx5^tm1.1Jse/Tbx5⁺
• Genetic Background: involves: 129/Sv * Black Swiss

mortality/aging

perinatal lethality, incomplete penetrance ( J:71845 )

• Background Sensitivity: on a 129/Sv background, only 10% of pups are alive and only 3 of those survive past weaning, however on a mixed 129/Sv and Black Swiss background, 40% die perinatally and those that survive 3 weeks live into adulthood

cardiovascular system

ostium primum atrial septal defect ( J:71845 )

• large atrial septal defects are seen in all adults and appear to arise from an absence or reduction of the anterior portion of the septum

• atrial septal defects are also seen in E16.5 embryos

dilated heart atrium ( J:71845 )

• both atria are dilated

ventricular septal defect ( J:71845 )

• variety of cardiac malformations seen, including a membranous and a muscular ventricular septal defect

perimembraneous ventricular septal defect ( J:71845 )

muscular ventricular septal defect ( J:71845 )

abnormal heart ventricle shape ( J:71845 )

• ventricles have a bulbous appearance

enlarged heart ( J:71845 )

pericardial effusion ( J:71845 )

• thoracic cavities of some E16.5 embryos contain pleural and pericardial effusions

abnormal impulse conducting system conduction ( J:71845 )

atrioventricular block ( J:71845 )

• instances of second degree atrioventricular block (failed propagation of an atrial impulse to the ventricles) are seen in 3 of 6 mice

prolonged PR interval ( J:71845 )

• indicates a delay in the time required for atrial impulses to reach the ventricles (first degree atrioventricular block)

sinoatrial block ( J:71845 )

• long sinoatrial pauses (transient failure of atrial impulse generation) in all mice

prolonged P wave ( J:71845 )

• P wave is broader, however QRS complexes and T waves are not different from wild-type

limbs/digits/tail

abnormal carpal bone morphology ( J:71845 )

• hypoplastic falciformis bones in the wrist

abnormal phalanx morphology ( J:71845 )

• phalangeal segments of the first forelimb digit are elongated

skeleton

abnormal carpal bone morphology ( J:71845 )

• hypoplastic falciformis bones in the wrist

abnormal phalanx morphology ( J:71845 )

• phalangeal segments of the first forelimb digit are elongated

homeostasis/metabolism

pericardial effusion ( J:71845 )

• thoracic cavities of some E16.5 embryos contain pleural and pericardial effusions

hydrops fetalis ( J:71845 )

• some E16.5 embryos are edematous with blood pooling in the extremities and the thoracic cavities contain pleural and pericardial effusions

growth/size/body

enlarged heart ( J:71845 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Holt-Oram syndrome		DOID:0060468	OMIM:142900	J:71845

Genotype
MGI:3617912

ht4

• Allelic Composition: Tbx5^tm1.1Jse/Tbx5⁺
• Genetic Background: involves: Black Swiss

limbs/digits/tail

abnormal digit morphology ( J:105332 )

• forelimb digit 1 elements are significantly longer than in wild-type mice

cardiovascular system

abnormal heart morphology ( J:105332 )

• the severity of congenital heart defects is less than in mice that are also heterozygous for Sall4 and after 15 generations of out breeding to Black Swiss no ventricular septal defects are seen

Genotype
MGI:3617911

cx5

• Allelic Composition: Sall4^Gt(XE027)Byg/Sall4⁺; Tbx5^tm1.1Jse/Tbx5⁺
• Genetic Background: involves: 129P2/OlaHsd * Black Swiss * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:105332 )

• about 80% die between E11.5 and the perinatal period

limbs/digits/tail

abnormal digit morphology ( J:105332 )

• forelimb digit 1 elements are significantly longer than in either single heterozygote

• elongation of digit 1 is detectable at E12.5

abnormal forelimb morphology ( J:105332 )

• occasional severe truncation of the anterior forelimb

cardiovascular system

abnormal atrioventricular valve morphology ( J:105332 )

abnormal mitral valve morphology ( J:105332 )

• the mitral valve was displaced downward toward the apex of the heart

common atrium ( J:105332 )

• in some cases the atrial septum is absent

perimembraneous ventricular septal defect ( J:105332 )

muscular ventricular septal defect ( J:105332 )

• perimembranous and multiple muscular septal defects are seen