Phenotypes associated with this allele

• Allele Symbol: Acvr1^tm1Glh
• Allele Name: targeted mutation 1, David J Goldhamer
• Allele ID: MGI:6140231
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Acvr1^tm1Glh/Acvr1^tm1Vk Gt(ROSA)26Sor^tm1.2(CAG-EGFP)Glh/Gt(ROSA)26Sor^+ Tg(Tek-cre)1Ywa/0	involves: 129 * C57BL/6 * FVB/N * SJL	MGI:7278774
cn2	Acvr1^tm1Glh/Acvr1^+ Gt(ROSA)26Sor^tm1.2(CAG-EGFP)Glh/Gt(ROSA)26Sor^+ Tg(Pdgfra-cre)1Clc/0	involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * FVB/N	MGI:7278773
cn3	Acvr1^tm1Glh/Acvr1^+ Gt(ROSA)26Sor^tm1.2(CAG-EGFP)Glh/Gt(ROSA)26Sor^+ Tg(Tek-cre)1Ywa/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N * SJL	MGI:7278772
cn4	Acvr1^tm1Glh/Acvr1^+ Myod1^tm2.1(icre)Glh/Myod1^+	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:7278769
cn5	Acvr1^tm1Glh/Acvr1^+ Tg(Cdh5-cre)7Mlia/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:7278770

Genotype
MGI:7278774

cn1

• Allelic Composition: Acvr1^tm1Glh/Acvr1^tm1Vk; Gt(ROSA)26Sor^{tm1.2(CAG-EGFP)Glh}/Gt(ROSA)26Sor⁺; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N * SJL

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

homeostasis/metabolism

abnormal response to injury ( J:257905 )

• pinch injury of adult gastrocnemius muscle results in a 50-fold increase in heterotopic ossification volume compared to mice that have one wild-type allele of Acvr1

skeleton

increased bone ossification ( J:257905 )

• pinch injury of adult gastrocnemius muscle results in a 50-fold increase in heterotopic ossification volume compared to mice that have one wild-type allele of Acvr1

Genotype
MGI:7278773

cn2

• Allelic Composition: Acvr1^tm1Glh/Acvr1⁺; Gt(ROSA)26Sor^{tm1.2(CAG-EGFP)Glh}/Gt(ROSA)26Sor⁺; Tg(Pdgfra-cre)1Clc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * FVB/N

homeostasis/metabolism

abnormal response to injury ( J:257905 )

• skeletal muscle exhibits pinch injury-induced heterotopic ossification

skeleton

increased bone ossification ( J:257905 )

• spontaneous heterotopic ossification is seen infrequently in some 2-week-old mice and is present in all 4-week-old mice and extensive in all surviving mice by 6 weeks of age

• heterotopic ossification is seen in the musculature, tendons, and ligaments at diverse locations

• skeletal elements resulting from spontaneous heterotopic ossification are derived almost exclusively from recombined cells

• all mice treated with an anti-activin A mAb prior to onset of heterotopic ossification for 4 weeks survive to 6 weeks of age and 8 of 9 mice show no evidence of heterotopic ossification and no spontaneous heterotopic ossification is not seen in treated 16-week-old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:257905

Genotype
MGI:7278772

cn3

• Allelic Composition: Acvr1^tm1Glh/Acvr1⁺; Gt(ROSA)26Sor^{tm1.2(CAG-EGFP)Glh}/Gt(ROSA)26Sor⁺; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N * SJL

homeostasis/metabolism

abnormal response to injury ( J:257905 )

• pinch injury of adult hindlimb skeletal muscle results in heterotopic ossification in 100% of mice; heterotopic skeletal lesions show that lesional tissue is typically embedded in muscle and associated soft tissues, although close apposition or fusion with limb skeletal elements is sometimes seen

• cardiotoxin-mediated injury of skeletal muscle also results in heterotopic ossification, except that this less localized injury stimulus sometimes results in tendon/ligament heterotopic ossification

• unlike in controls, regenerated muscle fibers are rarely seen in areas of lesion formation at 6 days post-injury, and instead injured muscle contains large numbers of chondrocytes and accumulations of fibroblastic cells

• by 14 days post-injury, most cartilage is replaced by bone instead of regenerated muscle fibers as in controls

• activin A injection lowers the threshold for injury-induced heterotopic ossification

• treatment with anti-activin A mAb effectively blocks injury-induced heterotopic ossification

skeleton

increased bone ossification ( J:257905 )

• spontaneous heterotopic ossification is seen as early as 5.5 months of age, and by 1 year of age, 12 of 15 mice develop spontaneous heterotopic ossification

• fibro/adipogenic progenitors represent the predominant cell-of-origin for both heterotopic cartilage and bone

• pinch injury or cardiotoxin-mediated injury of adult hindlimb skeletal muscle results in heterotopic ossification in 100% of mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:257905

Genotype
MGI:7278769

cn4

• Allelic Composition: Acvr1^tm1Glh/Acvr1⁺; Myod1^{tm2.1(icre)Glh}/Myod1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

skeleton

skeleton phenotype ( J:257905 )

N • pinch or cardiotoxin-mediated injury of the gastrocnemius or tibialis anterior hindlimb muscles of adults does not cause heterotopic ossification

Genotype
MGI:7278770

cn5

• Allelic Composition: Acvr1^tm1Glh/Acvr1⁺; Tg(Cdh5-cre)7Mlia/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

skeleton

skeleton phenotype ( J:257905 )

N • pinch-mediated injury of the gastrocnemius or tibialis anterior hindlimb muscles of adults does not cause heterotopic ossification