Phenotypes associated with this allele

• Allele Symbol: Tnfrsf11a^tm1.1Sral
• Allele Name: targeted mutation 1.1, Stuart H Ralston
• Allele ID: MGI:7427368
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnfrsf11a^tm1.1Sral/Tnfrsf11a^tm1.1Sral	B6.129P2(Cg)-Tnfrsf11a^tm1.1Sral	MGI:7427404
ht2	Tnfrsf11a^tm1.1Sral/Tnfrsf11a^+	B6.129P2(Cg)-Tnfrsf11a^tm1.1Sral	MGI:7427405

Genotype
MGI:7427404

hm1

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

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

mortality/aging

premature death ( J:312215 )

• mice exhibit reduced survival, with 31% of mice dying by 4 weeks of age

growth/size/body

absent incisors ( J:312215 )

• mice lack incisors by the time of weaning and have to be fed a soft food diet

decreased body size ( J:312215 )

craniofacial

absent incisors ( J:312215 )

• mice lack incisors by the time of weaning and have to be fed a soft food diet

skeleton

absent incisors ( J:312215 )

• mice lack incisors by the time of weaning and have to be fed a soft food diet

abnormal tibia morphology ( J:312215 )

• trabecular area and peripheral circumference of tibias are increased

increased long bone epiphyseal plate size ( J:312215 )

• expansion of the growth plate

abnormal long bone metaphysis morphology ( J:312215 )

• metaphyseal widening

abnormal bone structure ( J:312215 )

• bone marrow cavity is filled with mineralized cartilage

abnormal osteoclast differentiation ( J:312215 )

• bone marrow-derived macrophages fail to form osteoclasts in vitro in response to RANKL and M-CSF

decreased osteoclast cell number ( J:312215 )

• no osteoclasts are detected in bone sections indicating complete absence of osteoclasts

decreased compact bone thickness ( J:312215 )

• thinning of the cortex

abnormal trabecular bone morphology ( J:312215 )

• trabecular area of tibias is increased

increased trabecular bone volume ( J:312215 )

• higher trabecular bone volume/tissue volume ratio

increased bone trabecula number ( J:312215 )

decreased bone trabecular spacing ( J:312215 )

• lower trabecular separation

increased trabecular bone thickness ( J:312215 )

osteopetrosis ( J:312215 )

• mice become progressively unwell with age due to severe osteopetrosis

osteosclerosis ( J:312215 )

• sclerosis of the tibia

limbs/digits/tail

abnormal tibia morphology ( J:312215 )

• trabecular area and peripheral circumference of tibias are increased

immune system

abnormal osteoclast differentiation ( J:312215 )

• bone marrow-derived macrophages fail to form osteoclasts in vitro in response to RANKL and M-CSF

decreased osteoclast cell number ( J:312215 )

• no osteoclasts are detected in bone sections indicating complete absence of osteoclasts

hematopoietic system

abnormal osteoclast differentiation ( J:312215 )

• bone marrow-derived macrophages fail to form osteoclasts in vitro in response to RANKL and M-CSF

decreased osteoclast cell number ( J:312215 )

• no osteoclasts are detected in bone sections indicating complete absence of osteoclasts

cellular

abnormal osteoclast differentiation ( J:312215 )

• bone marrow-derived macrophages fail to form osteoclasts in vitro in response to RANKL and M-CSF

Genotype
MGI:7427405

ht2

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

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