Description

Strain Information

Former Names B6.Cg-Spp1tm1Blh/J    (Changed: 05-NOV-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10F?+N1F8 (04-DEC-07)   Donating Investigator Lucy Liaw,   Maine Medical Center Research Institute

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. 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.

All of the characterization of this mutant was performed while the mutant allele was on a mixed 129S6, Black Swiss background. The phenotype of the donated mutant, which is on a congenic C57BL/6 background, may vary.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 4 through 7 of the targeted gene. 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 (March 2003).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Spp1^tm1Blh/Spp1^tm1Blh

        B6.129S6(Cg)-Spp1^tm1Blh/J

• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:99574)
  • despite strong Spp1⁺ mRNA expression in wild-type testis cords and protein localization in the cytoplasm of Sertoli cells, testes from E13.5 homozygotes show no differences in the number or distribution of Sertoli, Leydig, or germ cells relative to wild-type testes

Spp1^tm1Blh/Spp1^tm1Blh

        B6.129S6-Spp1^tm1Blh

• nervous system phenotype
• abnormal dopaminergic neuron morphology (MGI Ref ID J:118432)
  • neuronal cell death in MPTP-treated homozygotes is comparable to sham-treated wildtype and significantly less than MPTP-treated wildtype, suggesting a protective effect
• abnormal striatum morphology (MGI Ref ID J:118432)
  • tyrosine hydroxylase (TH) positive nerve fibers in the striatum are decreased to a lesser extent in MPTP-treated homozygotes than in MPTP-treated wildtype mice
• abnormal substantia nigra morphology (MGI Ref ID J:118432)
  • MPTP-treated homozygotes exhibit an increase in the number of microglial cells, however, MPTP-treated wildtype mice exhibited a greater increase
  • numbers of GFAP-positive astrocytes increased in the MPTP-treated wildtype mice, but not in MPTP-treated homozygotes or sham-treated wildtype mice
  • astrocytic processes are longer in MPTP-treated homozygotes than in both MPTP-treated wildtype and sham-treated wildtype mice

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Spp1^tm1Blh/Spp1^tm1Blh

        involves: 129S6/SvEvTac * Black Swiss

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:46863)
  • under normal conditions, homozygotes are viable and fertile, with no apparent defects in growth, external morphology or behavior
  • importantly, unwounded skin from homozygotes displays normal tissue architecture and cell organization in the subepithelial, middermal, and deep dermal regions; differences in dermal organization become significant only in the context of the healing process
• homeostasis/metabolism phenotype
• abnormal wound healing (MGI Ref ID J:46863)
  • at 2 weeks after dermal incisional wounding, homozygotes exhibit reduced debridement throughout the wound site, esp. in the subepithelial dermis
  • in resolving wounds, the reforming matrix appears to be less organized in both the subepithelial and middermal regions
  • in the subepithelial and middermal zones, the organization of collagen fibrils and fibers is less distinct
  • in the deep reticular dermis, the collagen fibril diameter is significantly smaller; fibrils remain small, with a homogenous distribution at all wound levels
  • notably, homozygotes show no significant differences in tensile strength of healing incisional wounds relative to wild-type mice
• immune system phenotype
• abnormal macrophage recruitment (MGI Ref ID J:140014)
  • increased numbers of macrophage in the liver after infection
  • peritoneal exudate cells elevated at 72 hours after infection relative to controls
• altered susceptibility to infection (MGI Ref ID J:140014)
  • Mycobacterium bovis persists for at least 4 weeks after infections in livers and spleens at levels 10-40X those found in controls
  • bacterial loads are reduced by 12 weeks after infection
• granulomatous inflammation (MGI Ref ID J:140014)
  • overall greater burden of granulomas after infection than in controls, 3.1% of liver tissue compared to 1.1%

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Parkinson's Disease (resistance to MPTP)
Parkinson's Disease

Spp1^tm1Blh related

Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects
Inflammation

Internal/Organ Research
Wound Healing

Genes & Alleles

Gene & Allele Information

Allele Symbol		Spp1tm1Blh
Allele Name		targeted mutation 1, Brigid L Hogan
Allele Type		Targeted (knock-out)
Common Name(s)		Eta-1; OPN-; Opn-; eta1;
Mutation Made By		Lucy Liaw,   Maine Medical Center Research Institute
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TL1/TL-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Spp1, secreted phosphoprotein 1
Chromosome		5
Gene Common Name(s)		44kDa bone phosphoprotein; AA960535; AI790405; Apl-1; BNSP; BSPI; ETA-1; Eta; MGC110940; OP; OPN; OSP; Opn; Opnl; Ric; Spp-1; activation protein lymphocyte 1; bone sialoprotein 1; early T lymphocyte activation; expressed sequence AA960535; expressed sequence AI790405; minopontin; osteopontin; osteopontin-like protein; rickettsia tsutsugamushi resistance;
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. [MGI Ref ID J:46863]

Genotyping

Genotyping Information

Genotyping Protocols

Spp1^tm1Blh, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Liaw L; Birk DE; Ballas CB; Whitsitt JS; Davidson JM; Hogan BL. 1998. Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101(7):1468-78. [PubMed: 9525990]  [MGI Ref ID J:46863]

Additional References

Speer MY; McKee MD; Guldberg RE; Liaw L; Yang HY; Tung E; Karsenty G; Giachelli CM. 2002. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 196(8):1047-55. [PubMed: 12391016]  [MGI Ref ID J:79746]

Spp1^tm1Blh related

Abel B; Freigang S; Bachmann MF; Boschert U; Kopf M. 2005. Osteopontin is not required for the development of Th1 responses and viral immunity. J Immunol 175(9):6006-13. [PubMed: 16237095]  [MGI Ref ID J:119351]

Abel B; Kurrer M; Shamshiev A; Marty RR; Eriksson U; Gunthert U; Kopf M. 2006. The osteopontin - CD44 pathway is superfluous for the development of autoimmune myocarditis. Eur J Immunol 36(2):494-9. [PubMed: 16402410]  [MGI Ref ID J:113855]

Berman JS; Serlin D; Li X; Whitley G; Hayes J; Rishikof DC; Ricupero DA; Liaw L; Goetschkes M; O'Regan AW. 2004. Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice. Am J Physiol Lung Cell Mol Physiol 286(6):L1311-8. [PubMed: 14977630]  [MGI Ref ID J:108144]

Boskey AL; Spevak L; Paschalis E; Doty SB; McKee MD. 2002. Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone. Calcif Tissue Int 71(2):145-54. [PubMed: 12073157]  [MGI Ref ID J:81625]

Bruemmer D; Collins AR; Noh G; Wang W; Territo M; Arias-Magallona S; Fishbein MC; Blaschke F; Kintscher U; Graf K; Law RE; Hsueh WA. 2003. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 112(9):1318-31. [PubMed: 14597759]  [MGI Ref ID J:86531]

Duvall CL; Taylor WR; Weiss D; Wojtowicz AM; Guldberg RE. 2007. Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice. J Bone Miner Res 22(2):286-97. [PubMed: 17087627]  [MGI Ref ID J:133152]

Fujihara S; Yokozeki M; Oba Y; Higashibata Y; Nomura S; Moriyama K. 2006. Function and regulation of osteopontin in response to mechanical stress. J Bone Miner Res 21(6):956-64. [PubMed: 16753026]  [MGI Ref ID J:128094]

Hikita ST; Vistica BP; Jones HR; Keswani JR; Watson MM; Ericson VR; Ayoub GS; Gery I; Clegg DO. 2006. Osteopontin is proinflammatory in experimental autoimmune uveitis. Invest Ophthalmol Vis Sci 47(10):4435-43. [PubMed: 17003437]  [MGI Ref ID J:116272]

Hsieh YH; Juliana MM; Hicks PH; Feng G; Elmets C; Liaw L; Chang PL. 2006. Papilloma development is delayed in osteopontin-null mice: implicating an antiapoptosis role for osteopontin. Cancer Res 66(14):7119-27. [PubMed: 16849558]  [MGI Ref ID J:112122]

Ishii T; Ohshima S; Ishida T; Kawase I; Mima T; Tabunoki Y; Kobayashi H; Maeda M; Uede T; Liaw L; Kinoshita N; Saeki Y. 2004. Mice with osteopontin deletion remain predisposed to collagen-induced arthritis. Arthritis Rheum 50(2):669-71. [PubMed: 14872512]  [MGI Ref ID J:106166]

Kang JA; Zhou Y; Weis TL; Liu H; Ulaszek J; Satgurunathan N; Zhou L; van Besien K; Crispino J; Verma A; Low PS; Wickrema A. 2008. Osteopontin regulates actin cytoskeleton and contributes to cell proliferation in primary erythroblasts. J Biol Chem 283(11):6997-7006. [PubMed: 18174176]  [MGI Ref ID J:133795]

Kilic G; Wang J; Sosa-Pineda B. 2006. Osteopontin is a novel marker of pancreatic ductal tissues and of undifferentiated pancreatic precursors in mice. Dev Dyn 235(6):1659-67. [PubMed: 16518820]  [MGI Ref ID J:108608]

Maetzler W; Berg D; Schalamberidze N; Melms A; Schott K; Mueller JC; Liaw L; Gasser T; Nitsch C. 2007. Osteopontin is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model. Neurobiol Dis 25(3):473-82. [PubMed: 17188882]  [MGI Ref ID J:118432]

Mo L; Liaw L; Evan AP; Sommer AJ; Lieske JC; Wu XR. 2007. Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both. Am J Physiol Renal Physiol 293(6):F1935-43. [PubMed: 17898038]  [MGI Ref ID J:127526]

Myers DL; Harmon KJ; Lindner V; Liaw L. 2003. Alterations of arterial physiology in osteopontin-null mice. Arterioscler Thromb Vasc Biol 23(6):1021-8. [PubMed: 12714436]  [MGI Ref ID J:103050]

Nau GJ; Liaw L; Chupp GL; Berman JS; Hogan BL; Young RA. 1999. Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin. Infect Immun 67(8):4223-30. [PubMed: 10417195]  [MGI Ref ID J:140014]

Nomiyama T; Perez-Tilve D; Ogawa D; Gizard F; Zhao Y; Heywood EB; Jones KL; Kawamori R; Cassis LA; Tschop MH; Bruemmer D. 2007. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest 117(10):2877-88. [PubMed: 17823662]  [MGI Ref ID J:127389]

O'Regan AW; Hayden JM; Body S; Liaw L; Mulligan N; Goetschkes M; Berman JS. 2001. Abnormal pulmonary granuloma formation in osteopontin-deficient mice. Am J Respir Crit Care Med 164(12):2243-7. [PubMed: 11751194]  [MGI Ref ID J:103013]

Speer MY; McKee MD; Guldberg RE; Liaw L; Yang HY; Tung E; Karsenty G; Giachelli CM. 2002. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 196(8):1047-55. [PubMed: 12391016]  [MGI Ref ID J:79746]

Steitz SA; Speer MY; McKee MD; Liaw L; Almeida M; Yang H; Giachelli CM. 2002. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am J Pathol 161(6):2035-46. [PubMed: 12466120]  [MGI Ref ID J:113585]

Subramanian V; Krishnamurthy P; Singh K; Singh M. 2007. Lack of osteopontin improves cardiac function in streptozotocin-induced diabetic mice. Am J Physiol Heart Circ Physiol 292(1):H673-83. [PubMed: 16980342]  [MGI Ref ID J:119943]

Trueblood NA; Xie Z; Communal C; Sam F; Ngoy S; Liaw L; Jenkins AW; Wang J; Sawyer DB; Bing OH; Apstein CS; Colucci WS; Singh K. 2001. Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res 88(10):1080-7. [PubMed: 11375279]  [MGI Ref ID J:115399]

Weiss JM; Renkl AC; Maier CS; Kimmig M; Liaw L; Ahrens T; Kon S; Maeda M; Hotta H; Uede T; Simon JC. 2001. Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes. J Exp Med 194(9):1219-29. [PubMed: 11696588]  [MGI Ref ID J:119298]

Wesson JA; Johnson RJ; Mazzali M; Beshensky AM; Stietz S; Giachelli C; Liaw L; Alpers CE; Couser WG; Kleinman JG; Hughes J. 2003. Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules. J Am Soc Nephrol 14(1):139-47. [PubMed: 12506146]  [MGI Ref ID J:103140]

Wilson MJ; Liaw L; Koopman P. 2005. Osteopontin and related SIBLING glycoprotein genes are expressed by Sertoli cells during mouse testis development. Dev Dyn 233(4):1488-95. [PubMed: 15937924]  [MGI Ref ID J:99574]

Yoo KH; Thornhill BA; Forbes MS; Coleman CM; Marcinko ES; Liaw L; Chevalier RL. 2006. Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney Int 70(10):1735-41. [PubMed: 17003824]  [MGI Ref ID J:136483]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	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.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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