Phenotypes associated with this allele

• Allele Symbol: Tbx5^tm1Jse
• Allele Name: targeted mutation 1, Jonathan G Seidman
• Allele ID: MGI:2387850
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tbx5^tm1Jse/Tbx5^tm1Jse	involves: 129S/SvEv	MGI:3692756
ht2	Tbx5^tm1Jse/Tbx5^+	involves: 129S/SvEv	MGI:3692774
cn3	Tbx5^tm1Jse/Tbx5^tm1Jse Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6J * SJL/J	MGI:3623770
cn4	Tbx5^tm1Jse/Tbx5^tm1Jse Tg(Prrx1-cre/ERT2)1Mlgn/0	Not Specified	MGI:4442420
cn5	Tbx5^tm1Jse/Tbx5^tm1Jse Tg(Prrx1-cre/ERT2)1Mlgn/0 Tg(Scx-GFP)1Stzr/0	Not Specified	MGI:4442422
cn6	Pax3^tm1(cre)Joe/Pax3^+ Tbx5^tm1Jse/Tbx5^tm1Jse	Not Specified	MGI:4442424

Genotype
MGI:3692756

hm1

• Allelic Composition: Tbx5^tm1Jse/Tbx5^tm1Jse
• Genetic Background: involves: 129S/SvEv

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

mortality/aging

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

• die by E11.5

embryo

embryonic growth arrest ( J:112887 )

• growth arrested at E9.5

cardiovascular system

abnormal heart development ( J:112887 )

• heart development is arrested at E9

• although hearts begin to loop, both atrial and ventricular structures are hypoplastic, lacking the left/right distinctions that are normally apparent

abnormal heart atrium morphology ( J:112887 )

• hearts at E8.5 have hypoplastic sinoatrial structures (primitive inflow tract and atria)

heart atrium hypoplasia ( J:112887 )

abnormal heart left ventricle morphology ( J:112887 )

• hearts at E8.5 have a hypoplastic left ventricle

Genotype
MGI:3692774

ht2

• Allelic Composition: Tbx5^tm1Jse/Tbx5⁺
• Genetic Background: involves: 129S/SvEv

mortality/aging

postnatal lethality, incomplete penetrance ( J:112887 )

• about 27% die prior to weaning

cardiovascular system

atrial septal defect ( J:112887 )

• all mice exhibit atrial septal defects; atrial septal defects are smaller than in Tbx5^tm1.1Jse heterozygotes

• however, mice 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

prolonged PQ interval ( J:112887 )

• increase in PQ-interval duration at 12 weeks of age, indicative of first degree atrioventricular block; block is less severe than that seen in Tbx5^tm1.1Jse heterozygotes

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

Genotype
MGI:3623770

cn3

• Allelic Composition: Tbx5^tm1Jse/Tbx5^tm1Jse; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: C57BL/6J * SJL/J

growth/size/body

abnormal abdominal wall morphology ( J:217810 )

• due to absence of the sternum, the ribcage fails to close and associated herniation of internal organs and failure of abdominal body wall closure is seen

mortality/aging

perinatal lethality ( J:83258 )

limbs/digits/tail

absent apical ectodermal ridge ( J:83258 )

abnormal forelimb bud morphology ( J:83258 )

• no limb outgrowth and morphologically distinguishable apical ectodermal ridge are visible in the forelimb region; limb defect is manifest by E10.5

• cells of the prospective forelimb undergo extensive apoptosis by E9.5

absent forelimb buds ( J:83258 )

• at E10.5

absent forelimb ( J:83258 , J:217810 )

• forelimbs of newborns are completely absent, however the hindlimbs are unaffected (J:83258)

• some newborns have a small, rudimentary flap of skin on one side of the embryo where the forelimb would normally form (J:83258)

skeleton

absent clavicle ( J:83258 )

absent scapula ( J:83258 )

abnormal thoracic cage morphology ( J:83258 , J:217810 )

• ribcage fails to fuse (J:83258)

• due to absence of the sternum, the ribcage fails to close (J:217810)

absent sternum ( J:83258 , J:217810 )

• mice completely lack a sternum (J:217810)

• sternal bands do not form in E12.5-E13.5 embryos (J:217810)

embryo

absent apical ectodermal ridge ( J:83258 )

abnormal forelimb bud morphology ( J:83258 )

• no limb outgrowth and morphologically distinguishable apical ectodermal ridge are visible in the forelimb region; limb defect is manifest by E10.5

• cells of the prospective forelimb undergo extensive apoptosis by E9.5

absent forelimb buds ( J:83258 )

• at E10.5

Genotype
MGI:4442420

cn4

• Allelic Composition: Tbx5^tm1Jse/Tbx5^tm1Jse; Tg(Prrx1-cre/ERT2)1Mlgn/0
• Genetic Background: Not Specified

limbs/digits/tail

abnormal forelimb morphology ( J:157917 )

• at E16.5 in contrast to wild-type forelimbs where the spinodeltoidus (Spd), musculus triceps brachii longus (Tbl), and m triceps brachii lateralis (Tblt) muscles have specific origin and insertion sites, muscle bundles in the equivalent region of mutant limbs show a common origin at one focus and have split to form smaller muscle bundles that insert at aberrant sites when tamoxifen treatment is performed at E10.5; mispatterning of emerging muscles and ectopic splitting of nascent muscle bundles in observed by E13.5 with tamoxifen treatment at E10.5

• with tamoxifen treatment at E10.5, in the forelimb the m triceps brachii medialis (Tbm), Tbl, and Tblt, which insert on the olecranon process of the ulna in wild-type, show ectopic splitting into additional bundles which insert in the more distal shaft of the ulna

• zeugopodal muscles such as the m extensor digitorum communis (Edc) are ectopically split

• all limb musculature is affected

• limb muscle formation is unaffected if tamoxifen administration is done at E11.5

• terminal differentiation of limb muscle is not affected

abnormal limb development ( J:157917 )

Genotype
MGI:4442422

cn5

• Allelic Composition: Tbx5^tm1Jse/Tbx5^tm1Jse; Tg(Prrx1-cre/ERT2)1Mlgn/0; Tg(Scx-GFP)1Stzr/0
• Genetic Background: Not Specified

muscle

abnormal tendon morphology ( J:157917 )

• some tendon fibers connecting forearm muscles to skeletal elements in the handplate are thinner than in controls and some have fused together

• in forelimb, tendons develop functional entheses on the forming skeleton

limbs/digits/tail

abnormal forelimb morphology ( J:157917 )

• with tamoxifen treatment at E9.5, limbs display minor skeletal deformities similar to those in humans with Holt-Oram syndrome (triphalangeal thumb)

• muscle patterning is disrupted similarly to that with tamoxifen treatment at E10.5

• patterning of tendon fibers connecting forearm muscles to skeletal elements in the handplate is significantly disrupted compared to wild-type; fewer tendon fibers are present

• mispatterned muscles make functional myotendinous attachments to tendons

abnormal limb development ( J:157917 )

skeleton

abnormal tendon morphology ( J:157917 )

• some tendon fibers connecting forearm muscles to skeletal elements in the handplate are thinner than in controls and some have fused together

• in forelimb, tendons develop functional entheses on the forming skeleton

Genotype
MGI:4442424

cn6

• Allelic Composition: Pax3^tm1(cre)Joe/Pax3⁺; Tbx5^tm1Jse/Tbx5^tm1Jse
• Genetic Background: Not Specified

limbs/digits/tail

limbs/digits/tail phenotype ( J:157917 )

N • with conditional deletion of Tbx5 in myoblasts prior to migration to the limb field, muscle patterning is normal and resembles controls limb muscle patterns