Phenotypes Associated with This Genotype

Genotype
MGI:5881966

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

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

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