Phenotypes associated with this allele

• Allele Symbol: Acvr1^tm2.1Vlcg
• Allele Name: targeted mutation 2.1, Velocigene
• Allele ID: MGI:5763014
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	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
cn2	Acvr1^tm2.1Vlcg/Acvr1^+ Gt(ROSA)26Sor^tm3.1(cre/ERT2)Vlcg/Gt(ROSA)26Sor^+	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6NTac	MGI:5825038
cn3	Acvr1^tm2.1Vlcg/Acvr1^+ Tg(Prrx1-cre)1Cjt/0	involves: C57BL/6J * C57BL/6NTac * SJL/J	MGI:5881966

Genotype
MGI:5881968

cn1

• 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

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

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:5825038

cn2

• 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:5881966

cn3

• 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