Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N7pN1 Generation Definitions   Donating Investigator David Mangelsdorf,   UT Southwestern Medical Center

Description
In this strain a neomycin (neo) resistance cassette replaces exons 5-6 of the nuclear receptor subfamily 1, group H, member 2 (Nr1h2) gene, abolishing gene function. Homozygous are viable, fertile, and normal in size. Also known as liver X receptor beta (Lxrβ), Nr1h2 binds to retinoid X receptors (RXRα, RXRβ, RXRγ; NR2B1, NR2B2, and NR2B3) and is activated by oxysterols to regulate the expression of genes involved in cholesterol metabolism. . Homozygous Lxrβ^-/- mice lose their ability to appropriately regulate cholesterol, lipid, and carbohydrate metabolism, and have defects in immune function. These defects are more severe when combined with the knockout of Lxrα (available as Stock No. 013762). These mice may be useful for studying lipid and cholesterol metabolism, and regulation of the immune response.

Development
A targeting vector was designed to replace exons 5-6 encoding DNA-binding domain and the ligand-binding domains of the nuclear receptor subfamily 1, group H, member 2 (Nr1h2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6 mice. These mice were backcrossed at least 7 generations to a 129 background. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Nr1h2^tm1Djm allele

014633	B6.129S6-Nr1h2tm1Djm/J
014635	B6;129S-Nr1h2tm1Djm/J

View Strains carrying   Nr1h2^tm1Djm     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Nr1h2^tm1Djm/Nr1h2^tm1Djm

        involves: 129S6/SvEvTac

• integument phenotype
• thin epidermis
  • the epidermis of mutant mice is thinner with fewer proliferating cells in the basal layer compared to wild-type littermates   (MGI Ref ID J:89874)
  • treatment with oxysterol does not result in thickening of the epidermis unlike in wild-type littermates and Nr1h3^tm1Djm homozygotes   (MGI Ref ID J:89874)

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

Nr1h2^tm1Djm/Nr1h2^tm1Djm

        involves: 129S6/SvEvTac * C57BL/6

• mortality/aging
• increased sensitivity to induced morbidity/mortality
  • mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls   (MGI Ref ID J:81696)
• pregnancy-related premature death
  • occasionally mothers fail to expulse pups from uterine horns leading rarely to death   (MGI Ref ID J:120923)
• immune system phenotype
• increased susceptibility to bacterial infection
  • mice succumb to infection of Listeria monocytogenes 2-3 days earlier than controls   (MGI Ref ID J:81696)
• reproductive system phenotype
• abnormal Sertoli cell morphology
  • Sertoli cells have vacuoles containing cholesterol esters   (MGI Ref ID J:120913)
• abnormal myometrium morphology
  • vacuoles filled with cholesterol esters are present within the myoctes   (MGI Ref ID J:120923)
  • concentration of cholesterol esters are about 25-fold higher at 3 and 12 months of age   (MGI Ref ID J:120923)
• abnormal parturition
  • occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death   (MGI Ref ID J:120923)
• abnormal spermatogonia proliferation
  • proliferation of male germ cells is significantly decreased compared to controls   (MGI Ref ID J:120913)
• abnormal uterus physiology
  • myometrium muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin   (MGI Ref ID J:120923)
• endocrine/exocrine gland phenotype
• abnormal Sertoli cell morphology
  • Sertoli cells have vacuoles containing cholesterol esters   (MGI Ref ID J:120913)
• behavior/neurological phenotype
• hindlimb paralysis
  • occasionally mothers fail to expulse pups from uterine horns leading to hind-limb paralysis and rarely to death   (MGI Ref ID J:120923)
• muscle phenotype
• impaired smooth muscle contractility
  • myometrium (uterus) muscle has lower amplitudes of contraction compared to controls in response to pharmacological levels of oxytocin   (MGI Ref ID J:120923)
• cellular phenotype
• abnormal spermatogonia proliferation
  • proliferation of male germ cells is significantly decreased compared to controls   (MGI Ref ID J:120913)

View Research Applications

Research Applications

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

Cardiovascular Research
Hypocholesterolemia

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency

Internal/Organ Research
Liver Defects

Metabolism Research
Lipid Metabolism

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Nr1h2tm1Djm
Allele Name		targeted mutation 1, David J Mangelsdorf
Allele Type		Targeted (knock-out)
Common Name(s)		LXRbeta-;
Mutation Made By		David Mangelsdorf,   UT Southwestern Medical Center
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Nr1h2, nuclear receptor subfamily 1, group H, member 2
Chromosome		7
Gene Common Name(s)		AI194859; LXR-b; LXRB; LXRbeta; NER; NER-I; OR-1; RIP15; UNR; Unr; Unr2; expressed sequence AI194859; ubiquitously-expressed nuclear receptor; ubiquitously-expressed nuclear receptor 2;
Molecular Note		Insertion of a targeting vector replaced exons 5 and 6 with a neomycin resistance cassette creating a null allele. Exons 5 and 6 encode the DNA-binding and ligand-binding domains.

Genotyping

Genotyping Information

Genotyping Protocols

Nr1h2^tm1Djmalternate1, Standard PCR
Nr1h2^tm1Djm, Standard PCR
Nr1h2^tm1Djmalternate1,

Separated MCA

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Maisonpierre PC; Belluscio L; Friedman B; Alderson RF; Wiegand SJ; Furth ME; Lindsay RM; Yancopoulos GD. 1990. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5(4):501-9. [PubMed: 1688327]  [MGI Ref ID J:14634]

Additional References

Nr1h2^tm1Djm related

A-Gonzalez N; Bensinger SJ; Hong C; Beceiro S; Bradley MN; Zelcer N; Deniz J; Ramirez C; Diaz M; Gallardo G; de Galarreta CR; Salazar J; Lopez F; Edwards P; Parks J; Andujar M; Tontonoz P; Castrillo A. 2009. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 31(2):245-58. [PubMed: 19646905]  [MGI Ref ID J:151872]

Bensinger SJ; Bradley MN; Joseph SB; Zelcer N; Janssen EM; Hausner MA; Shih R; Parks JS; Edwards PA; Jamieson BD; Tontonoz P. 2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134(1):97-111. [PubMed: 18614014]  [MGI Ref ID J:145492]

Cha JY; Repa JJ. 2007. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem 282(1):743-51. [PubMed: 17107947]  [MGI Ref ID J:154828]

Cui G; Qin X; Wu L; Zhang Y; Sheng X; Yu Q; Sheng H; Xi B; Zhang JZ; Zang YQ. 2011. Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J Clin Invest 121(2):658-70. [PubMed: 21266776]  [MGI Ref ID J:171827]

Cummins CL; Volle DH; Zhang Y; McDonald JG; Sion B; Lefrancois-Martinez AM; Caira F; Veyssiere G; Mangelsdorf DJ; Lobaccaro JM. 2006. Liver X receptors regulate adrenal cholesterol balance. J Clin Invest 116(7):1902-12. [PubMed: 16823488]  [MGI Ref ID J:111742]

Denechaud PD; Bossard P; Lobaccaro JM; Millatt L; Staels B; Girard J; Postic C. 2008. ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver. J Clin Invest 118(3):956-64. [PubMed: 18292813]  [MGI Ref ID J:135655]

Henry-Berger J; Mouzat K; Baron S; Bernabeu C; Marceau G; Saru JP; Sapin V; Lobaccaro JM; Caira F. 2008. Endoglin (CD105) expression is regulated by the liver X receptor alpha (NR1H3) in human trophoblast cell line JAR. Biol Reprod 78(6):968-75. [PubMed: 18276933]  [MGI Ref ID J:140815]

Hernandez Vallejo SJ; Alqub M; Luquet S; Cruciani-Guglielmacci C; Delerive P; Lobaccaro JM; Kalopissis AD; Chambaz J; Rousset M; Lacorte JM. 2009. Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet. Am J Physiol Gastrointest Liver Physiol 296(4):G782-92. [PubMed: 19196952]  [MGI Ref ID J:149786]

Hong C; Bradley MN; Rong X; Wang X; Wagner A; Grijalva V; Castellani LW; Salazar J; Realegeno S; Boyadjian R; Fogelman AM; Van Lenten BJ; Reddy ST; Lusis AJ; Tangirala RK; Tontonoz P. 2012. LXRalpha is uniquely required for maximal reverse cholesterol transport and atheroprotection in ApoE-deficient mice. J Lipid Res 53(6):1126-33. [PubMed: 22454476]  [MGI Ref ID J:184910]

Hong C; Walczak R; Dhamko H; Bradley MN; Marathe C; Boyadjian R; Salazar JV; Tontonoz P. 2011. Constitutive activation of LXR in macrophages regulates metabolic and inflammatory gene expression: identification of ARL7 as a direct target. J Lipid Res 52(3):531-9. [PubMed: 21187453]  [MGI Ref ID J:173138]

Hsu JJ; Lu J; Huang MS; Geng Y; Sage AP; Bradley MN; Tontonoz P; Demer LL; Tintut Y. 2009. T0901317, an LXR agonist, augments PKA-induced vascular cell calcification. FEBS Lett 583(8):1344-8. [PubMed: 19327357]  [MGI Ref ID J:147981]

Joseph SB; Bradley MN; Castrillo A; Bruhn KW; Mak PA; Pei L; Hogenesch J; O'connell RM; Cheng G; Saez E; Miller JF; Tontonoz P. 2004. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 119(2):299-309. [PubMed: 15479645]  [MGI Ref ID J:93893]

Joseph SB; Castrillo A; Laffitte BA; Mangelsdorf DJ; Tontonoz P. 2003. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med 9(2):213-9. [PubMed: 12524534]  [MGI Ref ID J:81696]

Kalaany NY; Gauthier KC; Zavacki AM; Mammen PP; Kitazume T; Peterson JA; Horton JD; Garry DJ; Bianco AC; Mangelsdorf DJ. 2005. LXRs regulate the balance between fat storage and oxidation. Cell Metab 1(4):231-44. [PubMed: 16054068]  [MGI Ref ID J:129844]

Komuves LG; Schmuth M; Fowler AJ; Elias PM; Hanley K; Man MQ; Moser AH; Lobaccaro JM; Williams ML; Mangelsdorf DJ; Feingold KR. 2002. Oxysterol stimulation of epidermal differentiation is mediated by liver X receptor-beta in murine epidermis. J Invest Dermatol 118(1):25-34. [PubMed: 11851872]  [MGI Ref ID J:89874]

Koroskenyi K; Duro E; Pallai A; Sarang Z; Kloor D; Ucker DS; Beceiro S; Castrillo A; Chawla A; Ledent CA; Fesus L; Szondy Z. 2011. Involvement of adenosine A2A receptors in engulfment-dependent apoptotic cell suppression of inflammation. J Immunol 186(12):7144-55. [PubMed: 21593381]  [MGI Ref ID J:175472]

Kotti TJ; Ramirez DM; Pfeiffer BE; Huber KM; Russell DW. 2006. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci U S A 103(10):3869-74. [PubMed: 16505352]  [MGI Ref ID J:107142]

Kumar N; Wang H; Liu D; Collins S. 2009. Liver X receptor is a regulator of orphan nuclear receptor NOR-1 gene transcription in adipocytes. Int J Obes (Lond) 33(5):519-24. [PubMed: 19238156]  [MGI Ref ID J:151278]

Le Martelot G; Claudel T; Gatfield D; Schaad O; Kornmann B; Sasso GL; Moschetta A; Schibler U. 2009. REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol 7(9):e1000181. [PubMed: 19721697]  [MGI Ref ID J:153064]

Liu B; Li H; Repa JJ; Turley SD; Dietschy JM. 2008. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res 49(3):663-9. [PubMed: 18077828]  [MGI Ref ID J:133425]

Lund EG; Peterson LB; Adams AD; Lam MH; Burton CA; Chin J; Guo Q; Huang S; Latham M; Lopez JC; Menke JG; Milot DP; Mitnaul LJ; Rex-Rabe SE; Rosa RL; Tian JY; Wright SD; Sparrow CP. 2006. Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype. Biochem Pharmacol 71(4):453-63. [PubMed: 16325781]  [MGI Ref ID J:105722]

Makoukji J; Shackleford G; Meffre D; Grenier J; Liere P; Lobaccaro JM; Schumacher M; Massaad C. 2011. Interplay between LXR and Wnt/{beta}-Catenin Signaling in the Negative Regulation of Peripheral Myelin Genes by Oxysterols. J Neurosci 31(26):9620-9. [PubMed: 21715627]  [MGI Ref ID J:174058]

Martin LJ; Tremblay JJ. 2010. Nuclear receptors in leydig cell gene expression and function. Biol Reprod 83(1):3-14. [PubMed: 20375256]  [MGI Ref ID J:161974]

Mouzat K; Prod'homme M; Volle DH; Sion B; Dechelotte P; Gauthier K; Vanacker JM; Lobaccaro JM. 2007. Oxysterol nuclear receptor LXRbeta regulates cholesterol homeostasis and contractile function in mouse uterus. J Biol Chem 282(7):4693-701. [PubMed: 17166844]  [MGI Ref ID J:120923]

Ouvrier A; Alves G; Damon-Soubeyrand C; Marceau G; Cadet R; Janny L; Brugnon F; Kocer A; Pommier A; Lobaccaro JM; Drevet JR; Saez F. 2011. Dietary cholesterol-induced post-testicular infertility. PLoS One 6(11):e26966. [PubMed: 22073227]  [MGI Ref ID J:180996]

Ouvrier A; Cadet R; Vernet P; Lallier B; Chardigny JM; Lobaccaro JM; Drevet JR; Saez F. 2009. LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell specific manner. J Lipid Res 50:1766-1775. [PubMed: 19395734]  [MGI Ref ID J:153781]

Pascual-Garcia M; Carbo JM; Leon T; Matalonga J; Out R; Van Berkel T; Sarrias MR; Lozano F; Celada A; Valledor AF. 2011. Liver X receptors inhibit macrophage proliferation through downregulation of cyclins D1 and B1 and cyclin-dependent kinases 2 and 4. J Immunol 186(8):4656-67. [PubMed: 21398609]  [MGI Ref ID J:172455]

Patel R; Patel M; Tsai R; Lin V; Bookout AL; Zhang Y; Magomedova L; Li T; Chan JF; Budd C; Mangelsdorf DJ; Cummins CL. 2011. LXRbeta is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice. J Clin Invest 121(1):431-41. [PubMed: 21123945]  [MGI Ref ID J:171854]

Repa JJ; Li H; Frank-Cannon TC; Valasek MA; Turley SD; Tansey MG; Dietschy JM. 2007. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci 27(52):14470-80. [PubMed: 18160655]  [MGI Ref ID J:130969]

Repa JJ; Liang G; Ou J; Bashmakov Y; Lobaccaro JM; Shimomura I; Shan B; Brown MS; Goldstein JL; Mangelsdorf DJ. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta Genes Dev 14(22):2819-30. [PubMed: 11090130]  [MGI Ref ID J:65994]

Repa JJ; Turley SD; Lobaccaro JA; Medina J; Li L; Lustig K; Shan B; Heyman RA; Dietschy JM; Mangelsdorf DJ. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers [see comments] Science 289(5484):1524-9. [PubMed: 10968783]  [MGI Ref ID J:64343]

Spann NJ; Garmire LX; McDonald JG; Myers DS; Milne SB; Shibata N; Reichart D; Fox JN; Shaked I; Heudobler D; Raetz CR; Wang EW; Kelly SL; Sullards MC; Murphy RC; Merrill AH Jr; Brown HA; Dennis EA; Li AC; Ley K; Tsimikas S; Fahy E; Subramaniam S; Quehenberger O; Russell DW; Glass CK. 2012. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151(1):138-52. [PubMed: 23021221]  [MGI Ref ID J:188262]

Tangirala RK; Bischoff ED; Joseph SB; Wagner BL; Walczak R; Laffitte BA; Daige CL; Thomas D; Heyman RA; Mangelsdorf DJ; Wang X; Lusis AJ; Tontonoz P; Schulman IG. 2002. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc Natl Acad Sci U S A 99(18):11896-901. [PubMed: 12193651]  [MGI Ref ID J:125452]

Umetani M; Domoto H; Gormley AK; Yuhanna IS; Cummins CL; Javitt NB; Korach KS; Shaul PW; Mangelsdorf DJ. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med 13(10):1185-92. [PubMed: 17873880]  [MGI Ref ID J:129931]

Uppal H; Saini SP; Moschetta A; Mu Y; Zhou J; Gong H; Zhai Y; Ren S; Michalopoulos GK; Mangelsdorf DJ; Xie W. 2007. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology 45(2):422-32. [PubMed: 17256725]  [MGI Ref ID J:136468]

Valasek MA; Clarke SL; Repa JJ. 2007. Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPC1L1 expression in mouse. J Lipid Res 48(12):2725-35. [PubMed: 17726195]  [MGI Ref ID J:129975]

Viennois E; Esposito T; Dufour J; Pommier A; Fabre S; Kemeny JL; Guy L; Morel L; Lobaccaro JM; Baron S. 2012. Lxralpha regulates the androgen response in prostate epithelium. Endocrinology 153(7):3211-23. [PubMed: 22547570]  [MGI Ref ID J:188637]

Volle DH; Mouzat K; Duggavathi R; Siddeek B; Dechelotte P; Sion B; Veyssiere G; Benahmed M; Lobaccaro JM. 2007. Multiple roles of the nuclear receptors for oxysterols liver X receptor to maintain male fertility. Mol Endocrinol 21(5):1014-27. [PubMed: 17341595]  [MGI Ref ID J:120913]

Volle DH; Repa JJ; Mazur A; Cummins CL; Val P; Henry-Berger J; Caira F; Veyssiere G; Mangelsdorf DJ; Lobaccaro JM. 2004. Regulation of the aldo-keto reductase gene akr1b7 by the nuclear oxysterol receptor LXRalpha (liver X receptor-alpha) in the mouse intestine: putative role of LXRs in lipid detoxification processes. Mol Endocrinol 18(4):888-98. [PubMed: 14739254]  [MGI Ref ID J:89079]

Wang H; Zhang Y; Yehuda-Shnaidman E; Medvedev AV; Kumar N; Daniel KW; Robidoux J; Czech MP; Mangelsdorf DJ; Collins S. 2008. Liver X receptor alpha is a transcriptional repressor of the uncoupling protein 1 gene and the brown fat phenotype. Mol Cell Biol 28(7):2187-200. [PubMed: 18195045]  [MGI Ref ID J:134191]

Watanabe M; Houten SM; Wang L; Moschetta A; Mangelsdorf DJ; Heyman RA; Moore DD; Auwerx J. 2004. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113(10):1408-18. [PubMed: 15146238]  [MGI Ref ID J:120199]

Zelcer N; Khanlou N; Clare R; Jiang Q; Reed-Geaghan EG; Landreth GE; Vinters HV; Tontonoz P. 2007. Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc Natl Acad Sci U S A 104(25):10601-6. [PubMed: 17563384]  [MGI Ref ID J:122372]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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