Phenotypes Associated with This Genotype

Genotype
MGI:4868214

• Allelic Composition: Prkaca^tm1Gsm/Prkaca⁺; Prkar1a^tm1.1Lsk/Prkar1a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

neoplasm

neoplasm ( J:160299 )

N • mutants do not develop schwannomas or thyroid tumors

increased skeletal tumor incidence ( J:160299 , J:166728 )

• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes (J:160299)

• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age (J:160299)

• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma (J:160299)

• 13% of mutants develop osteochondromyoxoma (J:160299)

• cells from the bone lesions originate from an area proximal to the growth plate (J:160299)

• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies (J:160299)

• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts (J:160299)

• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells (J:166728)

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

increased osteochondroma incidence ( J:160299 )

• rare chondromas in the long bones

skeleton

increased skeletal tumor incidence ( J:160299 , J:166728 )

• mutants develop a greater number of osseous lesions and develop them earlier than single Prkar1a heterozygotes (J:160299)

• 90% of mutants exhibit bone lesions in the tail by 6 months and 100% by 9 months of age (J:160299)

• osseous lesions are seen starting around 3 months of age and vary from rare chondromas in the long bones and ubiquitous osteochondrodysplasia of vertebral bodies to occasional sarcoma (J:160299)

• 13% of mutants develop osteochondromyoxoma (J:160299)

• cells from the bone lesions originate from an area proximal to the growth plate (J:160299)

• cartilaginous metaplasia, chondromas, and osteochondrodysplasia are seen in marrow cavities of up to 1/3 of the long bones and most of the vertebral bodies (J:160299)

• lesions are hypercellular and contain more irregular cartilage or bone islands; proliferating cells are committed osteogenic but are not able to mature into osteoblasts (J:160299)

• mutants develop bone tumors with histological resemblance to those seen in humans with neonatal-onset multisystem inflammatory disease, with lesions derived from osteoblast progenitor cells (J:166728)

increased osteosarcoma incidence ( J:160299 )

• rare development of metastatic osteochondrosarcomas

increased osteochondroma incidence ( J:160299 )

• rare chondromas in the long bones

decreased bone mineral density ( J:160299 )

• overall bone mineralization density is lower than in wild-type mice

abnormal compact bone morphology ( J:160299 )

• in affected bones, normal cortical bone is replaced by mineralized material

abnormal periosteum morphology ( J:160299 )

• periosteum of affected bones is abnormal, with occasional cells from lesions crossing the periosteum into the extraosseous space and Sharpey fibers, characteristic of fibrous dysplasia, are observed

abnormal bone mineralization ( J:160299 )

• although the bone marrow is expanded by active osteoclastic activity, these cells are not able to mature into osteoblasts and mineralize the matrix resulting in undermineralization

• bones exhibit a lag between bone matrix formation and mineralization and abnormal coordination of these processes with bone resorption

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
CINCA Syndrome		DOID:0090029	OMIM:607115	J:166728