Phenotypes Associated with This Genotype

Genotype
MGI:5883024

• Allelic Composition: Tg(EEF1A1-Gnas*R201C)184Pabi/0
• Genetic Background: either: (involves: 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * FVB/N)

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

skeleton

abnormal skeleton morphology ( J:240241 )

• all mice develop fibrous dysplasia that progresses from an initial stage in which excess primary bone formation occurs at endosteal surfaces and within medullary cavities, to an intermediate stage during which enhanced remodeling occurs, and a final stage during which marrow fibrosis and overall bone deformation and/or fractures are established

• lesions in the tail vertebrae first appear at 2 months of age

• 70% of mice develop multiple lesions at other skeletal sites, resulting in a polyostotic pattern of skeletal disease

• femur is the second earliest and second most common site of involvement, followed by tibia, spine, humerus, acropodial short bones, cranium, ribs, and pelvis

• however, mice exhibit normal bone development and embryonic bone cell differentiation

abnormal bone marrow cavity morphology ( J:240241 )

• in intermediate lesions (2-6 months from appearance), the marrow cavity is obliterated or narrowed and distorted

• early skeletal changes result in narrow and distorted marrow cavities

• in late lesions, the internal bone architecture is effaced, such that the cortical bone and marrow cavity can no longer be discerned

increased internal diameter of femur ( J:240241 )

• in the femur, early lesions consist in localized endosteal thickening at the midshaft or the metadiaphyseal junction, with thickening extending proximally and distally progressively and lytic changes developing within the thickened bone

abnormal compact bone morphology ( J:240241 )

• intermediate lesions show large, focal structural gaps within an abnormally expanded cortical bone, however no fibrosis is seen

• vertebra show intracortical gaps at sites of ectopic intracortical remodeling

• in late lesions, the internal bone architecture is effaced, such that the cortical bone and marrow cavity can no longer be discerned

abnormal bone trabecula morphology ( J:240241 )

• early changes consist of endosteal thickening, associated with an excess of abnormal bone trabeculae leading to narrowed and distorted marrow cavities

• endosteal/medullary bone trabeculae are irregular in shape and mode of woven bone, do not contain a cartilage core (not endochondrally formed) and are separated from each other by a cellular tissue

• a characteristic Chinese writing pattern of abnormal bone trabeculae is seen in late lesions

exostosis ( J:240241 )

• increasing hyperostosis and deformity of vertebrae, which progresses steadily after 1 year of age

• distal metaphyses become hyperostotic and deformed after 1 year of age

osteosclerosis ( J:240241 )

• progressive sclerosis in vertebrae, femur and other bones

abnormal bone mineralization ( J:240241 )

• excess bone of intermediate lesions is undermineralized

increased bone ossification ( J:240241 )

• early changes are dominated by abnormal and excessive bone formation, however excessive osteoclast activity is not seen at this time

abnormal bone remodeling ( J:240241 )

• a complex system of cement lines indicates the occurrence of multiple, recurrent cycles of intracortical remodeling in intermediate lesions

increased bone resorption ( J:240241 )

• intermediate lesions show prominent osteoclastic resorption

• intense osteoclastic activity extends up to the outer regions of the cortex causing microfractures

• florid osteocalstogenesis is obvious in resorptive lacunae

fragile skeleton ( J:240241 )

• spontaneous fractures of tail vertebrae in 9.1% of mice between 12 and 18 months

• spontaneous partial fractures of the distal femur are seen in 2 of 89 mice

• in late lesions (more than 10 months from appearance), individual bones are grossly deformed and/or fractured

limbs/digits/tail

increased internal diameter of femur ( J:240241 )

• in the femur, early lesions consist in localized endosteal thickening at the midshaft or the metadiaphyseal junction, with thickening extending proximally and distally progressively and lytic changes developing within the thickened bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
McCune Albright syndrome		DOID:1858	OMIM:174800	J:240241