Strain Name:

STOCK Psmb8tm1Hjf/J

Stock Number:

021201

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Availability:

Repository- Live

These LMP-7 KO mice may be useful for studying the role of the immunoproteasomes in T cell proliferation.

Description

Strain Information

Former Names B6.129-Psmb8tm1Hjf/J    (Changed: 18-NOV-13 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemHomozygote x Homozygote         (Female x Male)   05-MAY-14
Specieslaboratory mouse
GenerationN10+N1 (24-JUN-13)
Generation Definitions
 
Donating Investigator Alice Sijts,   University Utrecht

Description
In this strain, a neo cassette replaces exons 1-5 of the proteasome (prosome, macropain) subunit, beta type 8 (Psmb8) gene, abolishing gene expression. Psmb8 encodes low molecular mass polypeptide (LMP)-7, one of three catalytic immunosubunits that make up immunoproteasomes. In response to interferon-gamma (IFNγ) or tumor necrosis factor-alpha (TNF-α), cytokines that are released in the early stages of viral infections, catalytic immunosubunits are rapidly assembled to form immunoproteasomes. These specialized proteasomes are formed in most cells, including lymphoid cells, and have a relatively short life span of a few days. They process MHC class I Ag and play a role in CD8+ T cell proliferation. Homozygous mice are viable and fertile. These LMP-7-/- mice exhibit a reduced ability to process class I restricted antigens, leading to a 25-50% reduction of MHC class I cell surface antigens. These mice have a reduced number of functional T cells.

Development
A targeting vector was designed to replace exons 1-5 of the proteasome (prosome, macropain) subunit, beta type 8 (Psmb8) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females.

Another targeting vector was designed to replace exons 5-7 of the proteasome (prosome, macropain) subunit, beta type 10 (Psmb10) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females to generate a colony of Psmb10tm1Mgro knockout mice.

Mice carrying the mutations were crossed, and the resulting double mutants were backcrossed for at least 10 generations to C57BL/6 mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony. The Psmb10tm1Mgro allele was selected against, and was maintained as a separate strain (Stock No. 021607).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. Three of 27 markers throughout the genome, as well as 2 of 5 markers that determine C57BL/6J from C57BL/6N, were found to be segregating. One marker on chromosome 11 was from an unknown source. This suggests a contamination from an unknown source or incomplete backcross.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Autoinflammation, Lipodystrophy, and Dermatosis Syndrome; ALDD   (PSMB8)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Psmb8tm1Hjf/Psmb8tm1Hjf

        either: 129P2/OlaHsd or (involves: 129P2/OlaHsd * C57BL/6)
  • immune system phenotype
  • decreased level of surface class I molecules
    • reduced MHC class I cell surface antigens   (MGI Ref ID J:20012)
    • H-2K and H-2D are about equally reduced   (MGI Ref ID J:20012)
  • defective intracellular transport of class I molecules
    • splenocytes with reduced ability to process class I restricted antigens   (MGI Ref ID J:20012)

Psmb8tm1Hjf/Psmb8tm1Hjf

        involves: 129P2/OlaHsd * C57BL/6
  • tumorigenesis
  • altered tumor susceptibility
    • anti-tumor immunity against Lewis lung carcinoma cells induced by immunization with the DNA vaccine pUB-MUT1 is attenuated in mutant mice compared to comtrol B6   (MGI Ref ID J:108550)

Psmb8tm1Hjf/Psmb8tm1Hjf

        involves: 129P2/OlaHsd
  • immune system phenotype
  • abnormal dendritic cell antigen presentation
    • presentation of antigen by dendritic cells in vitro is less able to support proliferation of T cells   (MGI Ref ID J:180765)
  • decreased level of surface class I molecules
    • levels are decreased on splenic B cells and dendritic cells   (MGI Ref ID J:180765)
View Research Applications

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

Apoptosis Research

Cell Biology Research
Protein Processing
      degradation

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Psmb8tm1Hjf
Allele Name targeted mutation 1, H J Fehling
Allele Type Targeted (Null/Knockout)
Common Name(s) LMP-7-; LMP7-; beta5i-;
Strain of Origin129P2/OlaHsd
Gene Symbol and Name Psmb8, proteasome (prosome, macropain) subunit, beta type 8 (large multifunctional peptidase 7)
Chromosome 17
Gene Common Name(s) ALDD; D6S216; D6S216E; JMP; LMP7; Lmp-7; Lmp7; NKJO; PSMB5i; RING10; large multifunctional protease 7; low molecular weight polypeptide 7;
Molecular Note Exons 1-5, encoding the first 247 amino acids of the protein, were replaced with a neomycin resistance gene. [MGI Ref ID J:20012]

Genotyping

Genotyping Information

Genotyping Protocols

Psmb8tm1Hjf,

SEPARATED MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fehling HJ; Swat W; Laplace C; Kuhn R; Rajewsky K; Muller U; von Boehmer H. 1994. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science 265(5176):1234-7. [PubMed: 8066463]  [MGI Ref ID J:20012]

Additional References

Psmb8tm1Hjf related

Basler M; Dajee M; Moll C; Groettrup M; Kirk CJ. 2010. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. J Immunol 185(1):634-41. [PubMed: 20525886]  [MGI Ref ID J:161616]

Basler M; Lauer C; Moebius J; Weber R; Przybylski M; Kisselev AF; Tsu C; Groettrup M. 2012. Why the structure but not the activity of the immunoproteasome subunit low molecular mass polypeptide 2 rescues antigen presentation. J Immunol 189(4):1868-77. [PubMed: 22772448]  [MGI Ref ID J:189764]

Basler M; Youhnovski N; Van Den Broek M; Przybylski M; Groettrup M. 2004. Immunoproteasomes down-regulate presentation of a subdominant T cell epitope from lymphocytic choriomeningitis virus. J Immunol 173(6):3925-34. [PubMed: 15356141]  [MGI Ref ID J:92742]

Brosch S; Tenzer S; Akkad N; Lorenz B; Schild H; von Stebut E. 2012. Priming of Leishmania-reactive CD8+ T cells in vivo does not require LMP7-containing immunoproteasomes. J Invest Dermatol 132(4):1302-5. [PubMed: 22277939]  [MGI Ref ID J:185242]

Caudill CM; Jayarapu K; Elenich L; Monaco JJ; Colbert RA; Griffin TA. 2006. T cells lacking immunoproteasome subunits MECL-1 and LMP7 hyperproliferate in response to polyclonal mitogens. J Immunol 176(7):4075-82. [PubMed: 16547243]  [MGI Ref ID J:129878]

Chou B; Hiromatsu K; Okano S; Ishii K; Duan X; Sakai T; Murata S; Tanaka K; Himeno K. 2012. Antiangiogenic tumor therapy by DNA vaccine inducing aquaporin-1-specific CTL based on ubiquitin-proteasome system in mice. J Immunol 189(4):1618-26. [PubMed: 22802414]  [MGI Ref ID J:189740]

Deol P; Zaiss DM; Monaco JJ; Sijts AJ. 2007. Rates of processing determine the immunogenicity of immunoproteasome-generated epitopes. J Immunol 178(12):7557-62. [PubMed: 17548590]  [MGI Ref ID J:148594]

Duan X; Hisaeda H; Shen J; Tu L; Imai T; Chou B; Murata S; Chiba T; Tanaka K; Fehling HJ; Koga T; Sueishi K; Himeno K. 2006. The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells. Int Immunol 18(5):679-87. [PubMed: 16569681]  [MGI Ref ID J:108550]

Duan X; Imai T; Chou B; Tu L; Himeno K; Suzue K; Hirai M; Taniguchi T; Okada H; Shimokawa C; Hisaeda H. 2013. Resistance to malaria by enhanced phagocytosis of erythrocytes in LMP7-deficient mice. PLoS One 8(3):e59633. [PubMed: 23527234]  [MGI Ref ID J:199379]

Ferrington DA; Roehrich H; Chang AA; Huang CW; Maldonado M; Bratten W; Rageh AA; Heuss ND; Gregerson DS; Nelson EF; Yuan C. 2013. Corneal wound healing is compromised by immunoproteasome deficiency. PLoS One 8(1):e54347. [PubMed: 23365662]  [MGI Ref ID J:195798]

Hensley SE; Zanker D; Dolan BP; David A; Hickman HD; Embry AC; Skon CN; Grebe KM; Griffin TA; Chen W; Bennink JR; Yewdell JW. 2010. Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses. J Immunol 184(8):4115-22. [PubMed: 20228196]  [MGI Ref ID J:159882]

Huber EM; Basler M; Schwab R; Heinemeyer W; Kirk CJ; Groettrup M; Groll M. 2012. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell 148(4):727-38. [PubMed: 22341445]  [MGI Ref ID J:181547]

Hussong SA; Kapphahn RJ; Phillips SL; Maldonado M; Ferrington DA. 2010. Immunoproteasome deficiency alters retinal proteasome's response to stress. J Neurochem 113(6):1481-90. [PubMed: 20345760]  [MGI Ref ID J:163575]

Hussong SA; Roehrich H; Kapphahn RJ; Maldonado M; Pardue MT; Ferrington DA. 2011. A novel role for the immunoproteasome in retinal function. Invest Ophthalmol Vis Sci 52(2):714-23. [PubMed: 20881299]  [MGI Ref ID J:171555]

Hutchinson S; Sims S; O'Hara G; Silk J; Gileadi U; Cerundolo V; Klenerman P. 2011. A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS One 6(2):e14646. [PubMed: 21304910]  [MGI Ref ID J:170911]

Joeris T; Schmidt N; Ermert D; Krienke P; Visekruna A; Kuckelkorn U; Kaufmann SH; Steinhoff U. 2012. The proteasome system in infection: impact of beta5 and LMP7 on composition, maturation and quantity of active proteasome complexes. PLoS One 7(6):e39827. [PubMed: 22768135]  [MGI Ref ID J:187908]

Kalim KW; Basler M; Kirk CJ; Groettrup M. 2012. Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. J Immunol 189(8):4182-93. [PubMed: 22984077]  [MGI Ref ID J:190652]

Kimura HJ; Chen CY; Tzou SC; Rocchi R; Landek-Salgado MA; Suzuki K; Kimura M; Rose NR; Caturegli P. 2009. Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice. PLoS One 4(11):e7857. [PubMed: 19924240]  [MGI Ref ID J:155418]

Kincaid EZ; Che JW; York I; Escobar H; Reyes-Vargas E; Delgado JC; Welsh RM; Karow ML; Murphy AJ; Valenzuela DM; Yancopoulos GD; Rock KL. 2012. Mice completely lacking immunoproteasomes show major changes in antigen presentation. Nat Immunol 13(2):129-35. [PubMed: 22197977]  [MGI Ref ID J:180765]

Kremer M; Henn A; Kolb C; Basler M; Moebius J; Guillaume B; Leist M; Van den Eynde BJ; Groettrup M. 2010. Reduced immunoproteasome formation and accumulation of immunoproteasomal precursors in the brains of lymphocytic choriomeningitis virus-infected mice. J Immunol 185(9):5549-60. [PubMed: 20881186]  [MGI Ref ID J:165187]

Moebius J; van den Broek M; Groettrup M; Basler M. 2010. Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice. Eur J Immunol 40(12):3439-49. [PubMed: 21108466]  [MGI Ref ID J:174578]

Muchamuel T; Basler M; Aujay MA; Suzuki E; Kalim KW; Lauer C; Sylvain C; Ring ER; Shields J; Jiang J; Shwonek P; Parlati F; Demo SD; Bennett MK; Kirk CJ; Groettrup M. 2009. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781-7. [PubMed: 19525961]  [MGI Ref ID J:151526]

Nathan JA; Spinnenhirn V; Schmidtke G; Basler M; Groettrup M; Goldberg AL. 2013. Immuno- and constitutive proteasomes do not differ in their abilities to degrade ubiquitinated proteins. Cell 152(5):1184-94. [PubMed: 23452861]  [MGI Ref ID J:193666]

Nussbaum AK; Rodriguez-Carreno MP; Benning N; Botten J; Whitton JL. 2005. Immunoproteasome-deficient mice mount largely normal CD8+ T cell responses to lymphocytic choriomeningitis virus infection and DNA vaccination. J Immunol 175(2):1153-60. [PubMed: 16002717]  [MGI Ref ID J:155667]

Opitz E; Koch A; Klingel K; Schmidt F; Prokop S; Rahnefeld A; Sauter M; Heppner FL; Volker U; Kandolf R; Kuckelkorn U; Stangl K; Kruger E; Kloetzel PM; Voigt A. 2011. Impairment of immunoproteasome function by beta5i/LMP7 subunit deficiency results in severe enterovirus myocarditis. PLoS Pathog 7(9):e1002233. [PubMed: 21909276]  [MGI Ref ID J:183191]

Osterloh P; Linkemann K; Tenzer S; Rammensee HG; Radsak MP; Busch DH; Schild H. 2006. Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses. Proc Natl Acad Sci U S A 103(13):5042-7. [PubMed: 16549793]  [MGI Ref ID J:107657]

Palmowski MJ; Gileadi U; Salio M; Gallimore A; Millrain M; James E; Addey C; Scott D; Dyson J; Simpson E; Cerundolo V. 2006. Role of immunoproteasomes in cross-presentation. J Immunol 177(2):983-90. [PubMed: 16818754]  [MGI Ref ID J:134948]

Pang KC; Sanders MT; Monaco JJ; Doherty PC; Turner SJ; Chen W. 2006. Immunoproteasome subunit deficiencies impact differentially on two immunodominant influenza virus-specific CD8+ T cell responses. J Immunol 177(11):7680-8. [PubMed: 17114438]  [MGI Ref ID J:140596]

Reis J; Hassan F; Guan XQ; Shen J; Monaco JJ; Papasian CJ; Qureshi AA; Van Way CW 3rd; Vogel SN; Morrison DC; Qureshi N. 2011. The immunoproteasomes regulate LPS-induced TRIF/TRAM signaling pathway in murine macrophages. Cell Biochem Biophys 60(1-2):119-26. [PubMed: 21455681]  [MGI Ref ID J:175955]

Robek MD; Garcia ML; Boyd BS; Chisari FV. 2007. Role of immunoproteasome catalytic subunits in the immune response to hepatitis B virus. J Virol 81(2):483-91. [PubMed: 17079320]  [MGI Ref ID J:153327]

Stohwasser R; Kuckelkorn U; Kraft R; Kostka S; Kloetzel PM. 1996. 20S proteasome from LMP7 knock out mice reveals altered proteolytic activities and cleavage site preferences. FEBS Lett 383(1-2):109-13. [PubMed: 8612775]  [MGI Ref ID J:32091]

Strehl B; Joeris T; Rieger M; Visekruna A; Textoris-Taube K; Kaufmann SH; Kloetzel PM; Kuckelkorn U; Steinhoff U. 2006. Immunoproteasomes are essential for clearance of Listeria monocytogenes in nonlymphoid tissues but not for induction of bacteria-specific CD8+ T cells. J Immunol 177(9):6238-44. [PubMed: 17056553]  [MGI Ref ID J:140518]

Tu L; Moriya C; Imai T; Ishida H; Tetsutani K; Duan X; Murata S; Tanaka K; Shimokawa C; Hisaeda H; Himeno K. 2009. Critical role for the immunoproteasome subunit LMP7 in the resistance of mice to Toxoplasma gondii infection. Eur J Immunol 39(12):3385-94. [PubMed: 19830724]  [MGI Ref ID J:155117]

Volkov A; Hagner S; Loser S; Alnahas S; Raifer H; Hellhund A; Garn H; Steinhoff U. 2013. beta5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma. PLoS One 8(4):e60565. [PubMed: 23593249]  [MGI Ref ID J:200031]

Xing Y; Jameson SC; Hogquist KA. 2013. Thymoproteasome subunit-beta5T generates peptide-MHC complexes specialized for positive selection. Proc Natl Acad Sci U S A 110(17):6979-84. [PubMed: 23569244]  [MGI Ref ID J:196156]

Zaiss DM; de Graaf N; Sijts AJ. 2008. The proteasome immunosubunit multicatalytic endopeptidase complex-like 1 is a T-cell-intrinsic factor influencing homeostatic expansion. Infect Immun 76(3):1207-13. [PubMed: 18160473]  [MGI Ref ID J:131623]

de Graaf N; van Helden MJ; Textoris-Taube K; Chiba T; Topham DJ; Kloetzel PM; Zaiss DM; Sijts AJ. 2011. PA28 and the proteasome immunosubunits play a central and independent role in the production of MHC class I-binding peptides in vivo. Eur J Immunol 41(4):926-35. [PubMed: 21360704]  [MGI Ref ID J:175418]

van Helden MJ; de Graaf N; Bekker CP; Boog CJ; Zaiss DM; Sijts AJ. 2011. Immunoproteasome-deficiency has no effects on NK cell education, but confers lymphocytes into targets for NK cells in infected wild-type mice. PLoS One 6(8):e23769. [PubMed: 21887316]  [MGI Ref ID J:176150]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining the live Psmb8tm1Hjf colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   05-MAY-14
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Psmb8tm1Hjf  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Psmb8tm1Hjf  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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