Incidental Mutation 'P0012:Tnfrsf11b'
ID7544
Institutional Source Beutler Lab
Gene Symbol Tnfrsf11b
Ensembl Gene ENSMUSG00000063727
Gene Nametumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)
SynonymsOpg, OCIF, OPG, TR1, osteoclastogenesis inhibitory factor
MMRRC Submission 038266-MU
Accession Numbers

NCBI RefSeq: NM_008764.3; MGI:109587

Is this an essential gene? Possibly essential (E-score: 0.556) question?
Stock #P0012 (G1)
Quality Score
Status Validated
Chromosome15
Chromosomal Location54250619-54278484 bp(-) (GRCm38)
Type of Mutationsplice site
DNA Base Change (assembly) A to G at 54259798 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000078705 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000079772]
PDB Structure
Crystal structure of mouse RANKL-OPG complex [X-RAY DIFFRACTION]
Predicted Effect probably benign
Transcript: ENSMUST00000079772
SMART Domains Protein: ENSMUSP00000078705
Gene: ENSMUSG00000063727

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
TNFR 24 62 1.04e-2 SMART
TNFR 65 105 1.5e-8 SMART
TNFR 107 142 2.19e-10 SMART
TNFR 145 185 7.63e-1 SMART
DEATH 270 365 1.01e-9 SMART
Coding Region Coverage
  • 1x: 85.5%
  • 3x: 81.0%
  • 10x: 67.7%
  • 20x: 52.2%
Validation Efficiency 85% (579/685)
MGI Phenotype Strain: 2181227
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is an osteoblast-secreted decoy receptor that functions as a negative regulator of bone resorption. This protein specifically binds to its ligand, osteoprotegerin ligand, both of which are key extracellular regulators of osteoclast development. Studies of the mouse counterpart also suggest that this protein and its ligand play a role in lymph-node organogenesis and vascular calcification. Alternatively spliced transcript variants of this gene have been reported, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygote null mice have abnormal bone remodeling that results in severe osteoperosis with increased risk of fractures and growth retardation. Progressive hearing loss also results due to abnormal remodeling of the otic capsule. [provided by MGI curators]
Allele List at MGI

All alleles(4) : Targeted(4)

Other mutations in this stock
Total: 9 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamtsl3 A C 7: 82,574,257 N156T probably benign Het
Akap3 T C 6: 126,864,601 F61S possibly damaging Het
Arhgap1 T C 2: 91,670,263 V379A probably benign Het
Ces1h T C 8: 93,353,510 K459E unknown Het
Fbn1 T C 2: 125,369,321 probably benign Het
Hrh2 T C 13: 54,214,428 F141S probably benign Het
Igkv3-4 A T 6: 70,672,247 N77Y probably benign Het
Nup205 T C 6: 35,196,543 M496T possibly damaging Het
Tas2r124 T C 6: 132,755,540 Y271H possibly damaging Het
Other mutations in Tnfrsf11b
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00094:Tnfrsf11b APN 15 54259842 missense probably damaging 1.00
IGL00770:Tnfrsf11b APN 15 54254072 missense probably benign 0.16
IGL00774:Tnfrsf11b APN 15 54254072 missense probably benign 0.16
IGL02355:Tnfrsf11b APN 15 54252382 missense probably damaging 0.96
IGL02362:Tnfrsf11b APN 15 54252382 missense probably damaging 0.96
IGL02711:Tnfrsf11b APN 15 54256136 missense probably benign 0.01
IGL02870:Tnfrsf11b APN 15 54256027 missense probably benign 0.05
IGL03219:Tnfrsf11b APN 15 54254178 nonsense probably null
R1550:Tnfrsf11b UTSW 15 54254058 missense possibly damaging 0.94
R1813:Tnfrsf11b UTSW 15 54256097 nonsense probably null
R3840:Tnfrsf11b UTSW 15 54252082 missense probably damaging 0.99
R3910:Tnfrsf11b UTSW 15 54256182 splice site probably benign
R3911:Tnfrsf11b UTSW 15 54256182 splice site probably benign
R3912:Tnfrsf11b UTSW 15 54256182 splice site probably benign
R4299:Tnfrsf11b UTSW 15 54252095 missense probably benign
R4362:Tnfrsf11b UTSW 15 54256159 missense possibly damaging 0.94
R4363:Tnfrsf11b UTSW 15 54256159 missense possibly damaging 0.94
R5288:Tnfrsf11b UTSW 15 54278226 missense probably benign 0.00
R5653:Tnfrsf11b UTSW 15 54259866 missense probably damaging 1.00
R5753:Tnfrsf11b UTSW 15 54254059 missense possibly damaging 0.90
R6881:Tnfrsf11b UTSW 15 54254143 missense probably benign 0.00
R6997:Tnfrsf11b UTSW 15 54252374 missense probably damaging 0.99
R7704:Tnfrsf11b UTSW 15 54260101 missense probably benign 0.30
R7730:Tnfrsf11b UTSW 15 54254074 nonsense probably null
R8052:Tnfrsf11b UTSW 15 54252106 missense probably damaging 1.00
R8060:Tnfrsf11b UTSW 15 54254109 missense probably benign 0.38
X0025:Tnfrsf11b UTSW 15 54278235 missense probably benign 0.22
Protein Function and Prediction

Tumor necrosis factor receptor superfamily, member 11b [Tnfrsf11b; alternatively, osteoprotegerin (OPG) or osteoclastogenesis inhibitory factor (OCIF)], is a secreted protein that regulates bone resorption (1;2). It was determined that OPG regulates bone mass, osteoclast differentiation, inhibits the activation of mature osteoclasts, and stimulates osteoclast apoptosis (1).

Background

Mutations in TNFRSF11B cause juvenile Paget disease (OMIM: #239000), an osteopathic disorder that is characterized by rapidly remodeling woven bone, osteopenia, fractures, and progressive skeletal deformity [(3-5) and OMIM: *602643)].

 

Tnfrsf11btm1Eac/tm1Eac; MGI:2179712

involves: 129S4/SvJaeSor

These mice exhibit fractured diaphyses of long bones often seen in older mice, increased outer diameter of long bones (6).  These mice also have defective pro-B cell to pre-B cell transition, increased proliferative response to IL-7, increased number of peripheral B cells, and enhanced ability to stimulate T-cell proliferation (6).

 

Tnfrsf11btm1Khs/tm1Khs; MGI:2181227

B6.129P2-Tnfrsf11btm1Khs

This model has abnormal inner ear morphology and homozygotes display abnormal bone remodeling within the otic capsule with multiple foci showing osteoclastic bone resorption and formation of new bone, not observed in C57BL/6 control mice (7).  These mice also have decreased brainstem auditory evoked potential and increased susceptibility to age-related hearing loss (7).

 

Tnfrsf11btm1Khs/tm1Khs; MGI:2181227

involves: 129P2/OlaHsd * C57BL/6

This model exhibits partial postnatal lethality and postnatal growth retardation (8)  These animals also have abnormal bone structure, thinning in all three middle ear ossicles, and thinning of the incus body and the manubrium and processus brevis of the malleus (9).  The animals have abnormal osteoclast differentiation and decreased bone mineral density (8;9).  The animals also have increased osteoclast cell numbers in the metaphyseal region (10).

 

Tnfrsf11btm1Wss/tm1Wss; MGI:2183229

either: (involves: 129X1/SvJ * C57BL/6) or (involves: 129X1/SvJ * Black Swiss)

Approximately 15% of mice die prior to weaning likely from vertebral or endochondral bone fractures (11).  The parietal bones of the skull are thin and have increased porosity (11).  These mice exhibit decreased bone mineral density and osteoporotic by 1-2 months (11). The large arteries, including the aorta and in the kidney, exhibit some calcification as early as 2 weeks after birth and marked calcification by 2 months of age (11).

References
Posted On2012-10-04
Science WriterAnne Murray