Phenotypes Associated with This Genotype

Genotype
MGI:7427405

• Allelic Composition: Tnfrsf11a^tm1.1Sral/Tnfrsf11a⁺
• Genetic Background: B6.129P2(Cg)-Tnfrsf11a^tm1.1Sral

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

skeleton

abnormal osteoclast physiology ( J:312215 )

• percentage of surviving osteoclasts following withdrawal of RANKL is higher in cultures

abnormal tibia morphology ( J:312215 )

• most 12-month-old mice exhibit osteolytic lesions at the proximal tibia and distal femur close to the growth plate and at both lower femoral condyles and all develop lesions by 15 months of age

• 3 of 18 mice develop larger focal lesions in the tibial shaft of one limb; lesions show disorganized bone structure with a large number of osteoclasts and increased number of osteoblasts

• 12-month-old mice exhibit larger peripheral circumference, indicating bone enlargement

abnormal bone structure ( J:312215 )

• most 12-month-old mice exhibit osteolytic lesions at the proximal tibia and distal femur close to the growth plate and at both lower femoral condyles and all develop lesions by 15 months of age

• however, 4-month-old mice show normal trabecular bone density and structure, with no evidence of osteolytic bone lesions, and no differences in bone density

• mice administered zoledronic acid between 4 and 12 months of age show complete prevention of osteolytic lesion development

• however, no differences in skull bone morphology, width, length, or height are seen

abnormal osteoclast differentiation ( J:312215 )

• osteoclasts cultured from bone marrow cells are fewer in number and have a smaller number of nuclei and the percentage of larger osteoclasts is decreased in bone marrow cell cultures indicating a reduction in osteoclastogenesis

increased osteoclast cell number ( J:312215 )

• in the few mice that develop larger focal lesions in the tibia, lesions show a large number of osteoclasts

increased trabecular bone volume ( J:312215 )

• higher trabecular bone volume/tissue volume at 12 months of age

increased osteoblast cell number ( J:312215 )

• in the few mice that develop larger focal lesions in the tibia, lesions show an increased number of osteoblasts

increased bone trabecula number ( J:312215 )

• higher trabecular number at 12 months of age

decreased bone trabecular spacing ( J:312215 )

• trabecular separation is lower at 12 months of age

increased trabecular bone thickness ( J:312215 )

• increase in trabecular thickness at 12 months of age

limbs/digits/tail

abnormal tibia morphology ( J:312215 )

• most 12-month-old mice exhibit osteolytic lesions at the proximal tibia and distal femur close to the growth plate and at both lower femoral condyles and all develop lesions by 15 months of age

• 3 of 18 mice develop larger focal lesions in the tibial shaft of one limb; lesions show disorganized bone structure with a large number of osteoclasts and increased number of osteoblasts

• 12-month-old mice exhibit larger peripheral circumference, indicating bone enlargement

hematopoietic system

abnormal osteoclast differentiation ( J:312215 )

• osteoclasts cultured from bone marrow cells are fewer in number and have a smaller number of nuclei and the percentage of larger osteoclasts is decreased in bone marrow cell cultures indicating a reduction in osteoclastogenesis

increased osteoclast cell number ( J:312215 )

• in the few mice that develop larger focal lesions in the tibia, lesions show a large number of osteoclasts

abnormal osteoclast physiology ( J:312215 )

• percentage of surviving osteoclasts following withdrawal of RANKL is higher in cultures

immune system

abnormal osteoclast differentiation ( J:312215 )

• osteoclasts cultured from bone marrow cells are fewer in number and have a smaller number of nuclei and the percentage of larger osteoclasts is decreased in bone marrow cell cultures indicating a reduction in osteoclastogenesis

increased osteoclast cell number ( J:312215 )

• in the few mice that develop larger focal lesions in the tibia, lesions show a large number of osteoclasts

abnormal osteoclast physiology ( J:312215 )

• percentage of surviving osteoclasts following withdrawal of RANKL is higher in cultures

homeostasis/metabolism

decreased tumor necrosis factor (ligand) superfamily member 11 level ( J:312215 )

• mice show lower serum levels of RANKL at 4 months of age

• however, serum levels of P1NP or CTX-I are normal

cellular

abnormal osteoclast differentiation ( J:312215 )

• osteoclasts cultured from bone marrow cells are fewer in number and have a smaller number of nuclei and the percentage of larger osteoclasts is decreased in bone marrow cell cultures indicating a reduction in osteoclastogenesis

growth/size/body

growth/size/body region phenotype ( J:312215 )

N • mice have a normal body size

mortality/aging

mortality/aging ( J:312215 )

N • mice are viable and have normal survival

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Paget's disease of bone		DOID:5408	OMIM:PS167250	J:312215