Homozygotes exhibit disorganized ultrastructural wound matrix remodeling and defective macrophage infiltration and accumulation at sites of injury and infection. Mutant macrophage response to mycobacteria infection and pulmonary granulomatous response and inflammation are impaired. This mutant mouse strain may be useful in studies of carcinogenesis, tissue remodeling, wound repair, fibrosis and granulomatous diseases.
Lucy Liaw, Maine Medical Center Research Institute
OPN- have a neo cassette replacing exons 4-7 of the secreted phosphoprotein 1 (Spp1) gene. No gene product (mRNA) is detected by RT-PCR analysis of embryonic fibroblasts and kidney. Immunohistochemical analysis of kidney and bone tissue also fails to detect gene product (protein). Homozygotes exhibit disorganized ultrastructural wound matrix remodeling and defective macrophage infiltration and accumulation at sites of injury and infection. Experimentally induced hyperoxaluria results in renal tubule deposition of calcium oxalate crystals. Accelerated ectopic calcification mineralization in soft tissues occurs after subcutaneous implantation of glutaraldehyde-fixed aortic valve tissue. Mutant macrophage response to mycobacteria infection and pulmonary granulomatous response and inflammation are impaired. According to a recent publication (Hsieh et al 2006 Cancer Res 2006 66:7119-27), mutant mice treated with a skin chemical carcinogenesis protocol show a marked decrease both in tumor/papilloma incidence and multiplicity compared with wildtype. This mutant mouse strain may be useful in studies of tissue remodeling, wound repair, fibrosis and granulomatous diseases.
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 of these C57BL/6-congenic mice could vary from that originally described on a mixed 129S6, Black Swiss genetic background. We may modify the strain description if necessary as published results become available.
The OPN- targeting vector was designed to replace exons 4-7 of the secreted phosphoprotein 1 (Spp1) gene with neomycin resistance and herpes simplex virus thymidine kinase genes. The construct was electroporated into 129S6/SvEvTac derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to outbred Black Swiss, maintained on the mixed Black Swiss;129S6 background and then backcrossed to C57BL/6 for 10 generations by the donating lab (March 2003; see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 43 markers, on Chromosome 8, was segregating.
|Allele Name||targeted mutation 1, Brigid L Hogan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Brigid L Hogan; Spp1tm1Blh|
|Gene Symbol and Name||Spp1, secreted phosphoprotein 1|
|Gene Synonym(s)||44kDa bone phosphoprotein; expressed sequence AA960535; activation protein lymphocyte 1; BNSP; bone sialoprotein 1; BSPI; Apl-1; minopontin; Apl-1; AI790405; Spp-1; Ric; AA960535; Opn; Opnl; early T lymphocyte activation; OP; Opnl; osteopontin; osteopontin-like protein; Spp-1; Ric; 2ar; Eta; OPN; expressed sequence AI790405; OSP; rickettsia tsutsugamushi resistance; ETA-1; osteopontin-like protein; Opn|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A PGK neomycin resistance cassette replaced exons 4-7 of the Spp1 gene. No Spp1 transcript was detected by RT-PCR in embryonic fibroblasts or adult kidney from homozygous mutant animals. Spp1 transcript was not detected in homozygous mutant animals by in situ hybridization. Immunohistochemistry studies of adult kidney and bone did not detect protein in homozygous mutant mice.|
|Mutations Made By|| |
Lucy Liaw, Maine Medical Center Research Institute
This strain originated on a mixed Black Swiss, 129S6 background and has been backcrossed to C57BL/6 for at least 10 generations (March 2003). The strain is maintained as a homozygote.
When using the OPN KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004936 in your Materials and Methods section.
|Heterozygous for Spp1<tm1Blh>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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