Phenotypes Associated with This Genotype

Genotype
MGI:5788426

• Allelic Composition: Tg(TNFSF11)5519Edou/0
• Genetic Background: involves: C57BL/6J * CBA/J

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

adipose tissue

increased bone marrow adipose tissue amount ( J:233240 )

• progressive increase in adipocyte numbers in bone marrow that is apparent from the 3rd month of age

• increase in marrow adiposity is inversely correlated with bone marrow cellularity form 6 months of age

skeleton

increased bone marrow adipose tissue amount ( J:233240 )

• progressive increase in adipocyte numbers in bone marrow that is apparent from the 3rd month of age

• increase in marrow adiposity is inversely correlated with bone marrow cellularity form 6 months of age

increased osteoclast cell number ( J:233240 )

• increase in the number of giant osteoclasts at the epiphysis and the mid-diaphysis cortical region in 3 month old mice

• abundant osteoclasts are present within the cortical bone area

short femur ( J:233240 )

• femoral length is modestly decreased in 3 month old mice

increased diameter of femur ( J:233240 )

• femurs show an increase in the bone marrow volume and the cortical total volume, indicating an increase in bone width

abnormal compact bone morphology ( J:233240 )

• severe intracortical porosity at 3 months of age

• cortical porosity near growth plate is increased more than at mid-diaphysis

• progressive increase in cortical bone loss

• trabecularization of the cortical bone

decreased compact bone volume ( J:233240 )

• 26% decrease in cortical bone volume

• 38% decrease in cortical bone volume fraction

decreased compact bone thickness ( J:233240 )

• 48% decrease in cortical thickness

abnormal bone trabecula morphology ( J:233240 )

• trabecular bone loss is already seen by 4 weeks of age

decreased bone trabecula number ( J:233240 )

• almost complete absence of trabeculae by 3 months of age

osteoporosis ( J:233240 )

• severe bone loss that is already seen in the first month of age

• the metaphyseal regions of the distal femur and the proximal tibia are osteoporotic, showing an almost complete absence of trabeculae by 3 months of age

• treatment with denosumab, a human monoclonal antibody against human TNFSF11, inhibits bone resorption and reverses osteopporosis

abnormal cartilage morphology ( J:233240 )

• accumulation of cartilaginous remnants mainly in the epiphysis of 4 week old mice and the metaphysis of 3 month old mice, which gradually disappear

abnormal epiphyseal plate morphology ( J:233240 )

• cellular density in the resting/proliferation zones of growth plates is increased

• mice show a progressive growth plate loss, evident at 3 months of age, which almost disappears by 10 months

abnormal bone remodeling ( J:233240 )

• increased bone remodeling and trabecularization of the cortical bone

increased bone resorption ( J:233240 )

• abundant osteoclasts are present within the cortical bone area, indicating increased cortical bone remodeling

• levels of serum TRACP-5b are increased in 3 month old mice, indicating active bone resorption

decreased femur stiffness ( J:233240 )

• 70% reduction in stiffness of mid-diaphysis femurs from 3 month old mice

decreased bone strength ( J:233240 )

• mid-diaphysis femurs from 3 month old mice show reduced biomechanical properties, with a 58% reduction in ultimate force, 70% reduction in stiffness, and 45% reduction in plastic energy

hematopoietic system

increased osteoclast cell number ( J:233240 )

• increase in the number of giant osteoclasts at the epiphysis and the mid-diaphysis cortical region in 3 month old mice

• abundant osteoclasts are present within the cortical bone area

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:233240 )

• levels of serum alkaline phosphatase is increased 2.5-fold and 10-fold in 4 week and 3 month old mice, respectively

immune system

increased osteoclast cell number ( J:233240 )

• increase in the number of giant osteoclasts at the epiphysis and the mid-diaphysis cortical region in 3 month old mice

• abundant osteoclasts are present within the cortical bone area

limbs/digits/tail

short femur ( J:233240 )

• femoral length is modestly decreased in 3 month old mice

increased diameter of femur ( J:233240 )

• femurs show an increase in the bone marrow volume and the cortical total volume, indicating an increase in bone width

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteoporosis		DOID:11476	OMIM:166710	J:233240