Phenotypes Associated with This Genotype

Genotype
MGI:3052529

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

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

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 )

• AH interval is significantly longer in adults

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

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