Strain Name:

129-Dag1tm2Kcam/J

Stock Number:

006835

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Availability:

Cryopreserved - Ready for recovery

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Common Names: T30 x 129;    

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 Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
GenerationN6p+N1
Generation Definitions
 
Donating Investigator Kevin Campbell,   University of Iowa

Description
Mice that are homozygous for this floxed allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express cre recombinase, resulting offspring can have exon 2 of the targeted gene deleted in the cre-expressing tissue(s). As the targeted gene has three loxP sites, other genotypes may also result. These mutant mice may be useful in studying muscle disease and regeneration.

When bred to a strain expressing Cre recombinase under the control of the human glial fibrillary acidic protein promoter (GFAP) (see Stock No. 004600 for example), this mutant mouse strain may be useful in studies of brain abnormalities observed in congenital muscular dystrophies.

When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of retinal physiology.

When bred to mice carrying Tg(Mpz-cre)26Mes (see Stock No. 017927 for example) Cre recombinase expression in Schwann cells results in abnormal folding or the myelin sheath and demyelination.

Development
A targeting vector was used to introduce a loxP site downstream of exon 2 and insert a floxed neo cassette in the upstream intron. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. ES cells were injected into blastocysts. Chimeric animals were backcrossed to 129S1/SvImJ by the donating laboratory for six generations.

Control Information

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

Related Strains

Strains carrying   Dag1tm2Kcam allele
006834   B6.129-Dag1tm2Kcam/J
View Strains carrying   Dag1tm2Kcam     (1 strain)

Strains carrying other alleles of Dag1
009652   B6.129(Cg)-Dag1tm2.1Kcam/J
006836   B6.129-Dag1tm1Kcam/J
017975   B6.129S6-Dag1tm5Kcam/J
View Strains carrying other alleles of Dag1     (3 strains)

Additional Web Information

Introduction to Cre-lox technology

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.
Muscular Dystrophy-Dystroglycanopathy (limb-Girdle), Type C, 9; MDDGC9   (DAG1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Dag1tm2Kcam/Dag1tm2Kcam Tg(GFAP-cre)25Mes/0

        involves: 129S1/Sv * 129X1/SvJ * FVB/N   (conditional)
  • craniofacial phenotype
  • megacephaly   (MGI Ref ID J:86901)
  • nervous system phenotype
  • abnormal brain morphology
    • fusion of the cerebral interhemispheric fissure and adjacent cerebellar folia   (MGI Ref ID J:86901)
    • malformations resembling polymicrogyria   (MGI Ref ID J:86901)
    • abnormal cerebellar cortex morphology
      • cerebellar cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges   (MGI Ref ID J:86901)
    • abnormal cerebellum development
      • granule cells are observed in the subrarachnoid space during postnatal cerebellar development indicating aberrant migration of granule cells   (MGI Ref ID J:86901)
    • abnormal cerebral cortex morphology
      • cerebral cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges   (MGI Ref ID J:86901)
      • abnormal stratification in cerebral cortex
        • multifocal disarray of neuronal layering in the cerebral cortex   (MGI Ref ID J:86901)
    • abnormal hippocampus CA1 region morphology
      • some mutants show minor dispersion of neuronal cell bodies in the CA1 region   (MGI Ref ID J:86901)
    • abnormal hippocampus granule cell layer
      • some mutants show focal irregularities of the dentate granule cell layer in the hippocampus   (MGI Ref ID J:86901)
    • increased brain size
      • about 20% increase in brain size   (MGI Ref ID J:86901)
  • abnormal neuronal migration
    • cerebral, cerebellar and brain stem neuronal migration abnormalities   (MGI Ref ID J:86901)
  • abnormal subarachnoid space morphology
    • the normally open subarachnoid space is filled with heterotopic astrocytic and neuronal processes   (MGI Ref ID J:86901)
  • astrocytosis
    • GFAP-immunoreactive astrocytes are prominent in the cerebral cortex, indicating gliosis   (MGI Ref ID J:86901)
  • reduced long term potentiation
    • induction of long-term potentiation (LTP) by high-frequency stimulation is blunted in hippocampal slices, however baseline neurotransmission is unaffected and presynaptic neurotransmitter release is not affected   (MGI Ref ID J:86901)
  • vision/eye phenotype
  • abnormal rod electrophysiology
    • significantly reduced positive scotopic threshold response   (MGI Ref ID J:158199)
    • significantly increased negative scotopic threshold response   (MGI Ref ID J:158199)
    • the b-wave responses are severely attenuated   (MGI Ref ID J:158199)
  • cellular phenotype
  • abnormal neuronal migration
    • cerebral, cerebellar and brain stem neuronal migration abnormalities   (MGI Ref ID J:86901)

Dag1tm2Kcam/Dag1tm2Kcam Tg(Mpz-cre)26Mes/0

        involves: 129 * C57BL/6 * FVB/N   (conditional)
  • nervous system phenotype
  • abnormal action potential
    • reduced motor action potential amplitude   (MGI Ref ID J:137852)
  • abnormal myelin sheath morphology
    • abnormally folded myelin with loops, infolding and outfolding is seen in sciatic nerves   (MGI Ref ID J:137852)
  • abnormal nerve conduction   (MGI Ref ID J:137852)
    • decreased nerve conduction velocity   (MGI Ref ID J:137852)
  • demyelination
    • hypomyelination of the ventral roots   (MGI Ref ID J:137852)
    • decrease in myelination becomes evident with age and at 12 months of age includes signs of acute demyelination, myelin degeneration, macrophage infiltration, and remyelination   (MGI Ref ID J:137852)

Dag1tm2Kcam/Dag1tm2Kcam Tg(Nes-cre)1Kln/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL   (conditional)
  • vision/eye phenotype
  • abnormal rod electrophysiology
    • the positive scotopic threshold response is significantly reduced   (MGI Ref ID J:158199)
    • the b-wave responses are severely attenuated   (MGI Ref ID J:158199)
  • blindness
    • in the Morris water maze and visual cliff test   (MGI Ref ID J:158199)
  • buphthalmos   (MGI Ref ID J:158199)
  • corneal opacity
    • corneal opacities   (MGI Ref ID J:158199)
  • iris synechia
    • synechia of the iris and cornea   (MGI Ref ID J:158199)
  • microphthalmia   (MGI Ref ID J:158199)
  • mydriasis
    • pupils are dilated but responsive to light   (MGI Ref ID J:158199)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dag1tm2Kcam
Allele Name targeted mutation 2, Kevin P Campbell
Allele Type Targeted (Floxed/Frt)
Common Name(s) DG (lox); DG-flox; DGlox; Dag1L; Dag1flox; Dag1lox;
Mutation Made By Kevin Campbell,   University of Iowa
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Dag1, dystroglycan 1
Chromosome 9
Gene Common Name(s) 156DAG; A3a; AGRNR; D9Wsu13e; DAG; DG; DNA segment, Chr 9, Wayne State University 13, expressed; MDDGC7; MDDGC9; alpha-dystroglycan; beta-dystroglycan; dystrophin associated glycoprotein 1;
General Note Phenotypic Similarity to Human Syndrome: Type II (cobblestone) Lissencephaly (J:86901). Phenotypic Similarity to Human Syndrome: Cardiomyopathy, Dilated (J:169951).
Molecular Note Exon 2 was floxed by introducing a loxP site downstream of exon 2 and by inserting a floxed neo cassette into the upstream intron via homologous recombination. [MGI Ref ID J:78838]

Genotyping

Genotyping Information

Genotyping Protocols

Dag1tm2Kcam, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cohn RD; Henry MD; Michele DE; Barresi R; Saito F; Moore SA; Flanagan JD; Skwarchuk MW; Robbins ME; Mendell JR; Williamson RA; Campbell KP. 2002. Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration. Cell 110(5):639-48. [PubMed: 12230980]  [MGI Ref ID J:78838]

Additional References

Dag1tm2Kcam related

Beedle AM; Nienaber PM; Campbell KP. 2007. Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein complex. J Biol Chem 282(23):16713-7. [PubMed: 17452335]  [MGI Ref ID J:122734]

Berti C; Bartesaghi L; Ghidinelli M; Zambroni D; Figlia G; Chen ZL; Quattrini A; Wrabetz L; Feltri ML. 2011. Non-redundant function of dystroglycan and beta1 integrins in radial sorting of axons. Development 138(18):4025-37. [PubMed: 21862561]  [MGI Ref ID J:176243]

Court FA; Hewitt JE; Davies K; Patton BL; Uncini A; Wrabetz L; Feltri ML. 2009. A laminin-2, dystroglycan, utrophin axis is required for compartmentalization and elongation of myelin segments. J Neurosci 29(12):3908-19. [PubMed: 19321787]  [MGI Ref ID J:147273]

Court FA; Zambroni D; Pavoni E; Colombelli C; Baragli C; Figlia G; Sorokin L; Ching W; Salzer JL; Wrabetz L; Feltri ML. 2011. MMP2-9 cleavage of dystroglycan alters the size and molecular composition of Schwann cell domains. J Neurosci 31(34):12208-17. [PubMed: 21865464]  [MGI Ref ID J:176237]

Dacci P; Dina G; Cerri F; Previtali SC; Lopez ID; Lauria G; Feltri ML; Bolino A; Comi G; Wrabetz L; Quattrini A. 2010. Foot pad skin biopsy in mouse models of hereditary neuropathy. Glia 58(16):2005-16. [PubMed: 20878767]  [MGI Ref ID J:167389]

Han R; Kanagawa M; Yoshida-Moriguchi T; Rader EP; Ng RA; Michele DE; Muirhead DE; Kunz S; Moore SA; Iannaccone ST; Miyake K; McNeil PL; Mayer U; Oldstone MB; Faulkner JA; Campbell KP. 2009. Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of alpha-dystroglycan. Proc Natl Acad Sci U S A 106(31):12573-9. [PubMed: 19633189]  [MGI Ref ID J:152005]

Hu H; Li J; Zhang Z; Yu M. 2011. Pikachurin interaction with dystroglycan is diminished by defective O-mannosyl glycosylation in congenital muscular dystrophy models and rescued by LARGE overexpression. Neurosci Lett 489(1):10-5. [PubMed: 21129441]  [MGI Ref ID J:168704]

Jarad G; Miner JH. 2009. The Pax3-Cre transgene exhibits a rostrocaudal gradient of expression in the skeletal muscle lineage. Genesis 47(1):1-6. [PubMed: 18942111]  [MGI Ref ID J:144640]

Leonoudakis D; Singh M; Mohajer R; Mohajer P; Fata JE; Campbell KP; Muschler JL. 2010. Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. J Cell Sci 123(Pt 21):3683-92. [PubMed: 20940259]  [MGI Ref ID J:182923]

Levi S; Grady RM; Henry MD; Campbell KP; Sanes JR; Craig AM. 2002. Dystroglycan is selectively associated with inhibitory GABAergic synapses but is dispensable for their differentiation. J Neurosci 22(11):4274-85. [PubMed: 12040032]  [MGI Ref ID J:125567]

Liou LY; Walsh KB; Vartanian AR; Beltran-Valero de Bernabe D; Welch M; Campbell KP; Oldstone MB; Kunz S. 2010. Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse. PLoS One 5(3):e9915. [PubMed: 20369005]  [MGI Ref ID J:158951]

Michele DE; Kabaeva Z; Davis SL; Weiss RM; Campbell KP. 2009. Dystroglycan matrix receptor function in cardiac myocytes is important for limiting activity-induced myocardial damage. Circ Res 105(10):984-93. [PubMed: 19797173]  [MGI Ref ID J:169951]

Moore SA; Saito F; Chen J; Michele DE; Henry MD; Messing A; Cohn RD; Ross-Barta SE; Westra S; Williamson RA; Hoshi T; Campbell KP. 2002. Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418(6896):422-5. [PubMed: 12140559]  [MGI Ref ID J:86901]

Myshrall TD; Moore SA; Ostendorf AP; Satz JS; Kowalczyk T; Nguyen H; Daza RA; Lau C; Campbell KP; Hevner RF. 2012. Dystroglycan on radial glia end feet is required for pial basement membrane integrity and columnar organization of the developing cerebral cortex. J Neuropathol Exp Neurol 71(12):1047-63. [PubMed: 23147502]  [MGI Ref ID J:203478]

Nishimune H; Valdez G; Jarad G; Moulson CL; Muller U; Miner JH; Sanes JR. 2008. Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. J Cell Biol 182(6):1201-15. [PubMed: 18794334]  [MGI Ref ID J:142595]

Nodari A; Previtali SC; Dati G; Occhi S; Court FA; Colombelli C; Zambroni D; Dina G; Del Carro U; Campbell KP; Quattrini A; Wrabetz L; Feltri ML. 2008. Alpha6beta4 integrin and dystroglycan cooperate to stabilize the myelin sheath. J Neurosci 28(26):6714-9. [PubMed: 18579745]  [MGI Ref ID J:137852]

Noell S; Wolburg-Buchholz K; Mack AF; Beedle AM; Satz JS; Campbell KP; Wolburg H; Fallier-Becker P. 2011. Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet. Eur J Neurosci 33(12):2179-86. [PubMed: 21501259]  [MGI Ref ID J:176372]

Occhi S; Zambroni D; Del Carro U; Amadio S; Sirkowski EE; Scherer SS; Campbell KP; Moore SA; Chen ZL; Strickland S; Di Muzio A; Uncini A; Wrabetz L; Feltri ML. 2005. Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of ranvier. J Neurosci 25(41):9418-27. [PubMed: 16221851]  [MGI Ref ID J:101621]

Omori Y; Araki F; Chaya T; Kajimura N; Irie S; Terada K; Muranishi Y; Tsujii T; Ueno S; Koyasu T; Tamaki Y; Kondo M; Amano S; Furukawa T. 2012. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells. J Neurosci 32(18):6126-37. [PubMed: 22553019]  [MGI Ref ID J:184863]

Pawlisz AS; Feng Y. 2011. Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes. PLoS Biol 9(10):e1001172. [PubMed: 22028625]  [MGI Ref ID J:184033]

Saito F; Moore SA; Barresi R; Henry MD; Messing A; Ross-Barta SE; Cohn RD; Williamson RA; Sluka KA; Sherman DL; Brophy PJ; Schmelzer JD; Low PA; Wrabetz L; Feltri ML; Campbell KP. 2003. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron 38(5):747-58. [PubMed: 12797959]  [MGI Ref ID J:83782]

Satz JS; Ostendorf AP; Hou S; Turner A; Kusano H; Lee JC; Turk R; Nguyen H; Ross-Barta SE; Westra S; Hoshi T; Moore SA; Campbell KP. 2010. Distinct functions of glial and neuronal dystroglycan in the developing and adult mouse brain. J Neurosci 30(43):14560-72. [PubMed: 20980614]  [MGI Ref ID J:166208]

Satz JS; Philp AR; Nguyen H; Kusano H; Lee J; Turk R; Riker MJ; Hernandez J; Weiss RM; Anderson MG; Mullins RF; Moore SA; Stone EM; Campbell KP. 2009. Visual impairment in the absence of dystroglycan. J Neurosci 29(42):13136-46. [PubMed: 19846701]  [MGI Ref ID J:158199]

Singhal N; Xu R; Martin PT. 2012. Distinct contributions of Galgt1 and Galgt2 to carbohydrate expression and function at the mouse neuromuscular junction. Mol Cell Neurosci 51(3-4):112-26. [PubMed: 22982027]  [MGI Ref ID J:203675]

Stalnaker SH; Aoki K; Lim JM; Porterfield M; Liu M; Satz JS; Buskirk S; Xiong Y; Zhang P; Campbell KP; Hu H; Live D; Tiemeyer M; Wells L. 2011. Glycomic analyses of mouse models of congenital muscular dystrophy. J Biol Chem 286(24):21180-90. [PubMed: 21460210]  [MGI Ref ID J:173659]

Weir ML; Oppizzi ML; Henry MD; Onishi A; Campbell KP; Bissell MJ; Muschler JL. 2006. Dystroglycan loss disrupts polarity and {beta}-casein induction in mammary epithelial cells by perturbing laminin anchoring. J Cell Sci 119(Pt 19):4047-58. [PubMed: 16968749]  [MGI Ref ID J:113187]

Zhang Z; Zhang P; Hu H. 2011. LARGE Expression Augments the Glycosylation of Glycoproteins in Addition to alpha-Dystroglycan Conferring Laminin Binding. PLoS One 6(4):e19080. [PubMed: 21533062]  [MGI Ref ID J:172396]

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 & HusbandryWhen maintaining a live colony, homozygous mice may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

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

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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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