B6.129S4-Tnfrsf11b^tm1Eac/J

Stock number: 010672
Product name: opg-
Strain synonyms: B6-OPG
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Mice homozygous for this knockout of the osteoprotegerin develop severe osteoporosis and hematopoietic dysregulation. These OPG-mutant mice may be useful in studying bone biology, cardiovascular disease (regulation of atherosclerotic lesion development and calcification), modulating adaptive immunity, osteoimmunology, and autoimmune disease.

Detailed description

Mice homozygous for this osteoprotegerin (OPG)-mutant allele are viable and fertile. While a smaller transcript is made from the disrupted allele, the spliced product is predicted to be out of frame and result in a nonfunctional protein. OPG-deficient mice exhibit dysregulation of osteoclast production leading to drastic changes in the bone architecture; homozygotes develop severe osteoporosis, gross deformations in bone structure, decreased bone density, and altered long bones physical dimension. Hematopoietic, B lymphocyte, and dendritic cell functions are also dysregulated. It has been the experience of The Jackson Laboratory that animals homozygous for the Tnfrsf11b^tm1Eac exhibit 22-28% pre-wean mortality.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to insert a PGK-neo^r cassette into the Tnfrsf11b gene; eliminating the coding sequence for the first two Cys-rich repeats of the mature protein, 8 of 21 residues in the signal peptide, and the first half of the third Cys-rich region. The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to establish the colony. OPG-mutant mice were then backcrossed to C57BL/6J mice for approximately eight generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Allele

Symbol: Tnfrsf11b^tm1Eac
Name: targeted mutation 1, Edward A Clark
MGI accession ID: MGI:2179712
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: opg -
Marker symbol: Tnfrsf11b
Marker name: tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)
Marker synonyms: OCIF; OPG; osteoclastogenesis inhibitory factor; PDB5; TR1
Chromosome: 15
Strain of origin: 129S4/SvJaeSor
Molecular note: A neomycin resistance gene replaced a genomic fragment containing sequences encoding part of the signal peptide, the first two cysteine rich repeats and part of the third cysteine rich repeat. Northern blot analysis on total RNA derived from liver of homozygous mice demonstrated that a smaller transcript was expressed from this allele, but it is predicted to produce a nonfucntional protein.