Mouse Genome Informatics

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
phenotype observed in females
phenotype observed in males
N normal phenotype
• mutants do not develop schwannomas or thyroid tumors
• 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)
• rare development of metastatic osteochondrosarcomas
• rare chondromas in the long bones

• overall bone mineralization density is lower than in wild-type mice
• in affected bones, normal cortical bone is replaced by mineralized material
• 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
• 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
CINCA Syndrome; CINCA 607115 J:166728