Phenotypes associated with this allele

• Allele Symbol: Acvr1⁺
• Allele Name: wild type
• Allele ID: MGI:2437678
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Acvr1^tm1Emsh/Acvr1^+	C57BL/6-Acvr1^tm1Emsh	MGI:5471725
ht2	Acvr1^tm1.1(KOMP)Vlcg/Acvr1^+	C57BL/6N-Acvr1^tm1.1(KOMP)Vlcg/MbpMmucd	MGI:5705947
ht3	Acvr1^tm1Emsh/Acvr1^+	chimera involves: BALB/c * C57BL/6 * CD-1	MGI:5471728
cn4	Acvr1^tm2.1Vlcg/Acvr1^+ Gt(ROSA)26Sor^tm1(rtTA*M2)Jae/Gt(ROSA)26Sor^+ Tg(tetO-cre)1Jaw/0	involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6NTac	MGI:5881968
cn5	Acvr1^tm1Mak/Acvr1^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129 * C57BL/6	MGI:6414954
cn6	Acvr1^tm1Mak/Acvr1^+ Gt(ROSA)26Sor^tm1(Pik3ca*H1047R)Egan/Gt(ROSA)26Sor^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129 * C57BL/6 * FVB/N	MGI:6414964
cn7	Acvr1^tm1Mak/Acvr1^+ Gt(ROSA)26Sor^tm1(Pik3ca*H1047R)Egan/Gt(ROSA)26Sor^+ H3c2^tm1Mak/H3c2^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129 * C57BL/6 * FVB/N	MGI:6414961
cn8	Acvr1^tm1Mak/Acvr1^+ H3c2^tm1Mak/H3c2^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6414958
cn9	Acvr1^tm1Mak/Acvr1^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6414951
cn10	Acvr1^tm2.1Vlcg/Acvr1^+ Gt(ROSA)26Sor^tm3.1(cre/ERT2)Vlcg/Gt(ROSA)26Sor^+	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6NTac	MGI:5825038
cn11	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
cn12	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
cn13	Acvr1^tm1Glh/Acvr1^+ Myod1^tm2.1(icre)Glh/Myod1^+	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:7278769
cn14	Acvr1^tm1Glh/Acvr1^+ Tg(Cdh5-cre)7Mlia/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:7278770
cn15	Acvr1^tm2.1Vlcg/Acvr1^+ Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6J * C57BL/6NTac * SJL/J	MGI:5881966

Genotype
MGI:5471725

ht1

• Allelic Composition: Acvr1^tm1Emsh/Acvr1⁺
• Genetic Background: C57BL/6-Acvr1^tm1Emsh

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

mortality/aging

neonatal lethality, complete penetrance ( J:194134 )

• mice die within 24 hours of birth

Genotype
MGI:5705947

ht2

• Allelic Composition: Acvr1^{tm1.1(KOMP)Vlcg}/Acvr1⁺
• Genetic Background: C57BL/6N-Acvr1^{tm1.1(KOMP)Vlcg}/MbpMmucd
• Cell Lines: 13048A-A3

Data Sources

IMPC Data for Acvr1

homeostasis/metabolism

increased circulating total protein level ( J:211773 )

♀

IMPC - UCD

Genotype
MGI:5471728

ht3

• Allelic Composition: Acvr1^tm1Emsh/Acvr1⁺
• Genetic Background: chimera involves: BALB/c * C57BL/6 * CD-1

skeleton

abnormal phalanx morphology ( J:194134 )

• 13 of 27 mice exhibit shortened first metatarsal with a single or delta-shaped proximal phalanx

broad femur neck ( J:194134 )

• short broad femoral neck

short femur neck ( J:194134 )

• short broad femoral neck

short metatarsal bones ( J:194134 )

• 13 of 27 mice exhibit shortened first metatarsal with a single or delta-shaped proximal phalanx

increased osteochondroma incidence ( J:194134 )

• commonly in the proximal medial tibias, but also in the humerus and femur

abnormal cervical vertebrae morphology ( J:194134 )

• some mice exhibit fusion of the posterior facet joints of the subaxial cervical vertebrae

abnormal joint morphology ( J:194134 )

• malformation of costovertebral joints and ribs

• early degenerative joint disease

abnormal costovertebral joint morphology ( J:194134 )

• malformation of costovertebral joints

vertebral fusion ( J:194134 )

• fusion of thoracic and lumbar vertebrae

ectopic bone ( J:194134 )

• in skeletal muscles

• cardiotoxin-induced skeletal muscle injury triggers heterotropic ossification

• extraskeletal bone formation occurs by an endochondral process

abnormal joint mobility ( J:194134 )

• ankylosed joints at 6 to 8 weeks

cellular

increased apoptosis ( J:194134 )

• in degenerating muscle and connective tissue with abundant immune cell infiltration prior to ossified lesion formation

homeostasis/metabolism

edema ( J:194134 )

• swelling in soft tissue

immune system

increased inflammatory response ( J:194134 )

• inflammatory response followed by fibroproliferation in degenerating muscle and connective tissue

limbs/digits/tail

abnormal phalanx morphology ( J:194134 )

• 13 of 27 mice exhibit shortened first metatarsal with a single or delta-shaped proximal phalanx

broad femur neck ( J:194134 )

• short broad femoral neck

short femur neck ( J:194134 )

• short broad femoral neck

short metatarsal bones ( J:194134 )

• 13 of 27 mice exhibit shortened first metatarsal with a single or delta-shaped proximal phalanx

muscle

skeletal muscle degeneration ( J:194134 )

• due to apoptosis and possibly some necrosis

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:194134 )

• at 6 to 8 weeks, most mice exhibit severe physical disability with limited mobility and difficulty in movement

neoplasm

increased osteochondroma incidence ( J:194134 )

• commonly in the proximal medial tibias, but also in the humerus and femur

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:194134

Genotype
MGI:5881968

cn4

• Allelic Composition: Acvr1^tm2.1Vlcg/Acvr1⁺; Gt(ROSA)26Sor^{tm1(rtTA*M2)Jae}/Gt(ROSA)26Sor⁺; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6NTac

skeleton

increased bone ossification ( J:239136 )

• mice treated with doxycycline at 1 month of age for 3 days then injected with cardiotoxin into the quadriceps muscle to induce inflammation and muscle damage develop large heterotopic ossification tissue masses

• treatment of cardiotoxin-induced muscle injury with palovarotene diminishes heterotopic ossification formation by more than 80%

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:239136 )

• about 14 days after heterotopic ossification induction by injury in doxycycline treated mice, movement of affected legs is impaired

• treatment with palovarotene of mice with cardiotoxin-induced muscle injury rescues the impaired movement

Genotype
MGI:6414954

cn5

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129 * C57BL/6

nervous system

increased oligodendrocyte number ( J:285841 )

• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21

cellular

increased oligodendrocyte number ( J:285841 )

• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21

Genotype
MGI:6414964

cn6

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; Gt(ROSA)26Sor^{tm1(Pik3ca*H1047R)Egan}/Gt(ROSA)26Sor⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased brain tumor incidence ( J:285841 )

• most mice succumb to spontaneous brain tumors

increased glioma incidence ( J:285841 )

• tumors are high-grade diffuse gliomas

nervous system

increased brain tumor incidence ( J:285841 )

• most mice succumb to spontaneous brain tumors

increased glioma incidence ( J:285841 )

• tumors are high-grade diffuse gliomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
brain glioma		DOID:0060108		J:285841

Genotype
MGI:6414961

cn7

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; Gt(ROSA)26Sor^{tm1(Pik3ca*H1047R)Egan}/Gt(ROSA)26Sor⁺; H3c2^tm1Mak/H3c2⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased brain tumor incidence ( J:285841 )

• most mice succumb to spontaneous brain tumors, with a median survival of 419 days

increased glioma incidence ( J:285841 )

• tumors are high-grade diffuse gliomas

• tumors often infiltrate throughout many parts of the brain, particularly in the midbrain and thalamic regions

• tumors express markers of oligodendroglial origin

nervous system

increased brain tumor incidence ( J:285841 )

• most mice succumb to spontaneous brain tumors, with a median survival of 419 days

increased glioma incidence ( J:285841 )

• tumors are high-grade diffuse gliomas

• tumors often infiltrate throughout many parts of the brain, particularly in the midbrain and thalamic regions

• tumors express markers of oligodendroglial origin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
brain glioma		DOID:0060108		J:285841

Genotype
MGI:6414958

cn8

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; H3c2^tm1Mak/H3c2⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:285841 )

• partial early postnatal lethality

neoplasm

neoplasm ( J:285841 )

N • mice do not develop brain tumors

Genotype
MGI:6414951

cn9

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:285841 )

• some mice fail to gain normal body weight and die before weaning

behavior/neurological

ataxia ( J:285841 )

• surviving mice show moderate ataxia

muscle

muscle spasm ( J:285841 )

• surviving mice show spasms when disrupted during rest

nervous system

abnormal glial cell physiology ( J:285841 )

• glial cells exhibit increased growth

abnormal brain development ( J:285841 )

• marker analysis indicates the differentiation of oligodendroglial lineage cells is blocked and neuroglial progenitors are upregulated

abnormal brainstem morphology ( J:285841 )

• higher density of PDGFRA+ cells in brainstems

neoplasm

neoplasm ( J:285841 )

N • mice do not develop tumors

cellular

abnormal glial cell physiology ( J:285841 )

• glial cells exhibit increased growth

Genotype
MGI:5825038

cn10

• Allelic Composition: Acvr1^tm2.1Vlcg/Acvr1⁺; Gt(ROSA)26Sor^{tm3.1(cre/ERT2)Vlcg}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6NTac

skeleton

increased bone ossification ( J:234069 )

• as early as 2 weeks, tamoxifen-treated mice exhibit progressive, heterotopic ossification (HO) in the sternum, caudal vertebrae, hip joint and hindlimb resulting in fusion between the heterotropic bone and native skeletal elements

• mature heterotropic bone contain bone marrow and resemble normal bone

• however, treatment with broad-acting BMP and activin blockers ACVR2A-Fc and ACVR2B-Fc, alone or in combination, inhibits or ameliorates HO phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:234069

Genotype
MGI:7278773

cn11

• 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

cn12

• 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

cn13

• 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

cn14

• 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

Genotype
MGI:5881966

cn15

• Allelic Composition: Acvr1^tm2.1Vlcg/Acvr1⁺; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: C57BL/6J * C57BL/6NTac * SJL/J

skeleton

increased chondrocyte proliferation ( J:239136 )

• growth plates contain a higher number of proliferating chondrocytes in 2 week old mice

decreased length of long bones ( J:239136 )

• long bone elongation is impaired

• lengths of bones do not appear to be proportionally reduced

• palovarontene treatment protects long bone length

short humerus ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short radius ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short femur ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short tibia ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

abnormal skeleton development ( J:239136 )

• proliferating chondrocytes do not advance through the growth plate zones at normal rates; while control proliferating chondrocytes transition from the proliferative/prehypertrophic zones to the hypertrophic zone within 36 hours, only a few mutant proliferative chondrocytes are seen in the hypertrophic zone at this time

abnormal long bone epiphyseal plate morphology ( J:239136 )

• marker analysis indicates that overall growth plate homeostasis and function are defective in 14 day old mutants; hypertrophic differentiation of chondrocytes is disturbed and a delay in the cartilage to bone transition in the growth plates is seen

• however, the epiphyseal area is not grossly altered

decreased width of hypertrophic chondrocyte zone ( J:239136 )

• reduction in the height of the growth plate hypertrophic zone

increased bone ossification ( J:239136 )

• spontaneous heterotypic ossification becomes extensive by 1 month of age and is first detected in the hindlimbs at around P7 and then in the forelimbs beginning at around P14

• heterotypic ossification progressively increases over time

• treatment of nursing females with palovarotene reduces heterotypic ossification and improves skeletal malformations and growth of pups

limbs/digits/tail

abnormal digit morphology ( J:239136 )

• first digits of the hindlimbs are malformed

short humerus ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short radius ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short femur ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

short tibia ( J:239136 )

• length is reduced in 5 day old mice and growth retardation persists at 1 month

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:239136 )

• mutants exhibit severe movement impediment and difficulties

• palovarontene treatment improves mobility

cellular

increased chondrocyte proliferation ( J:239136 )

• growth plates contain a higher number of proliferating chondrocytes in 2 week old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fibrodysplasia ossificans progressiva		DOID:13374	OMIM:135100	J:239136