Strain Name:

B6.129X-Cxcr4tm1Qma/J

Stock Number:

004341

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Availability:

Cryopreserved - Ready for recovery

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

Former Names B6.129X-Cmkar4tm1Qma    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice that are homozygous null for the Cxcr4 gene die perinatally, with ~30% dying by embryonic day 18.5. Viable embryos are slightly smaller than wild type mice and exhibit vascular congestion in the kidneys, interstitial hemorrhages, and abnormalities in bone marrow and cerebellum. Homozygote embryos also show reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver and an absence of myelopoiesis in bone marrow. Histological examination reveals a distorted architecture in the tissues if the cerebellum, featuring an attenuated external granule cell layer and an ectopic placement of Purkinje cells.

Cxcr4 encodes a receptor commonly called CXCR4, the ligand of which is the chemokine stromal cell-derived factor 1 (SDF-1), an important regulator of hematopoietic cell development, migration and proliferation. CXCR4 also functions as a coreceptor for the entry of T-tropic strains of HIV-1 into CD4+ T cells.

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. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt exon 2 which codes the fourth transmembrane domain. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were crossed to C57BL/6J animals.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cxcr4
008767   B6.129P2-Cxcr4tm2Yzo/J
013608   C57BL/6J-Cxcr4b2b220Clo/J
View Strains carrying other alleles of Cxcr4     (2 strains)

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.
WHIM Syndrome   (CXCR4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Cxcr4tm1Qma/Cxcr4tm1Qma

        B6.129X-Cxcr4tm1Qma/J
  • muscle phenotype
  • abnormal muscle precursor cell migration
    • at E10.75 fewer hypaxial muscle progenitor cells reach the floor of the first branchial arch   (MGI Ref ID J:100909)
    • at E10.75, fewer progenitor cells are seen in the dorsal limb and this reduction is more pronounced distally (35%) than proximally (25%)   (MGI Ref ID J:100909)
    • however, no significant change in proliferation of muscle progenitors is seen   (MGI Ref ID J:100909)
  • abnormal myogenesis
    • at E10.75, the number of muscle cells (MyoD+) is reduced in the dorsal limb and this reduction is more pronounced distally than proximally; however at E13.5 the size and distribution of the muscle groups is not significantly different from control   (MGI Ref ID J:100909)
    • increased apoptosis is seen in the proximal domain of the dorsal limb   (MGI Ref ID J:100909)
    • however, no significant difference is seen in the size of the tongue muscle   (MGI Ref ID J:100909)
  • cellular phenotype
  • abnormal muscle precursor cell migration
    • at E10.75 fewer hypaxial muscle progenitor cells reach the floor of the first branchial arch   (MGI Ref ID J:100909)
    • at E10.75, fewer progenitor cells are seen in the dorsal limb and this reduction is more pronounced distally (35%) than proximally (25%)   (MGI Ref ID J:100909)
    • however, no significant change in proliferation of muscle progenitors is seen   (MGI Ref ID J:100909)

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

Cxcr4tm1Qma/Cxcr4tm1Qma

        involves: 129X1/SvJ
  • mortality/aging
  • partial perinatal lethality
    • about 1/3 of mice are dead at E18.5   (MGI Ref ID J:49070)
  • nervous system phenotype
  • abnormal cerebellum morphology
    • at E18.5, the cerebellum is disorganized with a highly distorted architecture and chromophillic cell clumps in the analage   (MGI Ref ID J:49070)
    • chromophillic clusters mostly contain early granule cell progenitors that are surrounded by Purkinje cells   (MGI Ref ID J:49070)
    • absent cerebellar foliation   (MGI Ref ID J:49070)
    • ectopic Purkinje cell   (MGI Ref ID J:49070)
    • thin external granule cell layer
      • at E18.5, the external granule cell layer is attenuated and irregular   (MGI Ref ID J:49070)
  • hematopoietic system phenotype
  • decreased bone marrow cell number
    • at E15.5, bone marrow is hypocellular and composed mostly of stromal cells and osteoblasts with a severe reduction in hematopoiesis   (MGI Ref ID J:49070)
    • at E18.5, hematopoiesis is still reduced but cellularity is similar to wild-type; however myeloid cells are virtually absent   (MGI Ref ID J:49070)
  • decreased pro-B cell number
    • at E18.5, the B220+/CD43+ pro-B cell population is severely reduced in the fetal liver (0.2% versus 7.0% in wild-type littermates); however T cell populations in the thymus are normal   (MGI Ref ID J:49070)
  • impaired myelopoiesis
    • at E18.5 in the fetal liver, myeloid cells are reduced to 25% of wild-type, myelopoiesis is reduced and a marked erythroid predominance is seen   (MGI Ref ID J:49070)
    • at E18.5, a marked reduction in myeloid cells is also seen in the spleen and myeloid cells are virtually absent from the bone marrow   (MGI Ref ID J:49070)
  • growth/size/body phenotype
  • decreased body size
    • viable homozygotes are smaller than littermates   (MGI Ref ID J:49070)
  • renal/urinary system phenotype
  • kidney hemorrhage
    • prominent interstitial hemorrhage   (MGI Ref ID J:49070)
  • kidney vascular congestion   (MGI Ref ID J:49070)
  • respiratory system phenotype
  • atelectasis
    • collapsed lungs   (MGI Ref ID J:49070)
  • immune system phenotype
  • decreased pro-B cell number
    • at E18.5, the B220+/CD43+ pro-B cell population is severely reduced in the fetal liver (0.2% versus 7.0% in wild-type littermates); however T cell populations in the thymus are normal   (MGI Ref ID J:49070)
  • impaired myelopoiesis
    • at E18.5 in the fetal liver, myeloid cells are reduced to 25% of wild-type, myelopoiesis is reduced and a marked erythroid predominance is seen   (MGI Ref ID J:49070)
    • at E18.5, a marked reduction in myeloid cells is also seen in the spleen and myeloid cells are virtually absent from the bone marrow   (MGI Ref ID J:49070)
  • cardiovascular system phenotype
  • kidney hemorrhage
    • prominent interstitial hemorrhage   (MGI Ref ID J:49070)
  • kidney vascular congestion   (MGI Ref ID J:49070)
View Research Applications

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

Cxcr4tm1Qma related

Developmental Biology Research
Internal/Organ Defects
      brain
      hematopoietic defects

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects
      hematopoietic development
Mechanisms of HIV Infection

Neurobiology Research
Cerebellar Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Cxcr4tm1Qma
Allele Name targeted mutation 1, Qing Ma
Allele Type Targeted (Null/Knockout)
Common Name(s) CXCR4-;
Mutation Made By Qing Ma,   Boston Children's Hospital
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Cxcr4, chemokine (C-X-C motif) receptor 4
Chromosome 1
Gene Common Name(s) CD184; Cmkar4; D2S201E; FB22; HM89; HSY3RR; LAP-3; LAP3; LCR1; LESTR; Mutant line 220; NPY3R; NPYR; NPYRL; NPYY3R; PB-CKR; Sdf1r; WHIM; b2b220Clo; chemokine (C-X-C) receptor 4; fusin;
Molecular Note A PGK-neomycin resistance cassette replaced sequences in exon 2 that encode the fourth transmembrane domain and a portion of the third extracellular domain. RT-PCR studies did not detect transcript in homozygous brain. [MGI Ref ID J:49070]

Genotyping

Genotyping Information

Genotyping Protocols

Cxcr4tm1Qma, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ma Q; Jones D; Borghesani PR; Segal RA; Nagasawa T; Kishimoto T; Bronson RT; Springer TA. 1998. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A 95(16):9448-53. [PubMed: 9689100]  [MGI Ref ID J:49070]

Additional References

Cxcr4tm1Qma related

Bodea GO; Spille JH; Abe P; Andersson AS; Acker-Palmer A; Stumm R; Kubitscheck U; Blaess S. 2014. Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system. Development 141(3):661-73. [PubMed: 24449842]  [MGI Ref ID J:208337]

Calderon L; Boehm T. 2011. Three chemokine receptors cooperatively regulate homing of hematopoietic progenitors to the embryonic mouse thymus. Proc Natl Acad Sci U S A 108(18):7517-22. [PubMed: 21502490]  [MGI Ref ID J:172050]

Christopher MJ; Liu F; Hilton MJ; Long F; Link DC. 2009. Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. Blood 114(7):1331-9. [PubMed: 19141863]  [MGI Ref ID J:151732]

Dziembowska M; Tham TN; Lau P; Vitry S; Lazarini F; Dubois-Dalcq M. 2005. A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors. Glia 50(3):258-69. [PubMed: 15756692]  [MGI Ref ID J:156051]

Eash KJ; Means JM; White DW; Link DC. 2009. CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions. Blood 113(19):4711-9. [PubMed: 19264920]  [MGI Ref ID J:150156]

Ghosh MC; Collins GD; Vandanmagsar B; Patel K; Brill M; Carter A; Lustig A; Becker KG; Wood WW 3rd; Emeche CD; French AD; O'Connell MP; Xu M; Weeraratna AT; Taub DD. 2009. Activation of Wnt5A signaling is required for CXC chemokine ligand 12-mediated T-cell migration. Blood 114(7):1366-73. [PubMed: 19520808]  [MGI Ref ID J:151723]

Hick AC; van Eyll JM; Cordi S; Forez C; Passante L; Kohara H; Nagasawa T; Vanderhaeghen P; Courtoy PJ; Rousseau GG; Lemaigre FP; Pierreux CE. 2009. Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1. BMC Dev Biol 9:66. [PubMed: 20003423]  [MGI Ref ID J:156021]

Hirbe AC; Rubin J; Uluckan O; Morgan EA; Eagleton MC; Prior JL; Piwnica-Worms D; Weilbaecher KN. 2007. Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone. Proc Natl Acad Sci U S A 104(35):14062-7. [PubMed: 17715292]  [MGI Ref ID J:124901]

Kaul M; Ma Q; Medders KE; Desai MK; Lipton SA. 2007. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ 14(2):296-305. [PubMed: 16841089]  [MGI Ref ID J:132342]

Li G; Adesnik H; Li J; Long J; Nicoll RA; Rubenstein JL; Pleasure SJ. 2008. Regional distribution of cortical interneurons and development of inhibitory tone are regulated by Cxcl12/Cxcr4 signaling. J Neurosci 28(5):1085-98. [PubMed: 18234887]  [MGI Ref ID J:131835]

Li G; Kataoka H; Coughlin SR; Pleasure SJ. 2009. Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. Development 136(2):327-35. [PubMed: 19103804]  [MGI Ref ID J:143512]

Ma Q; Jones D; Springer TA. 1999. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity 10(4):463-71. [PubMed: 10229189]  [MGI Ref ID J:110532]

Schwarting GA; Henion TR; Nugent JD; Caplan B; Tobet S. 2006. Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain. J Neurosci 26(25):6834-40. [PubMed: 16793890]  [MGI Ref ID J:109982]

Seo KW; Wang Y; Kokubo H; Kettlewell JR; Zarkower DA; Johnson RL. 2006. Targeted disruption of the DM domain containing transcription factor Dmrt2 reveals an essential role in somite patterning. Dev Biol 290(1):200-10. [PubMed: 16387292]  [MGI Ref ID J:104893]

Shichinohe H; Kuroda S; Yano S; Hida K; Iwasaki Y. 2007. Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct. Brain Res 1183:138-47. [PubMed: 17976542]  [MGI Ref ID J:128929]

Vasyutina E; Stebler J; Brand-Saberi B; Schulz S; Raz E; Birchmeier C. 2005. CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes Dev 19(18):2187-98. [PubMed: 16166380]  [MGI Ref ID J:100909]

Vianello F; Kraft P; Mok YT; Hart WK; White N; Poznansky MC. 2005. A CXCR4-dependent chemorepellent signal contributes to the emigration of mature single-positive CD4 cells from the fetal thymus. J Immunol 175(8):5115-25. [PubMed: 16210615]  [MGI Ref ID J:119123]

Walter DH; Haendeler J; Reinhold J; Rochwalsky U; Seeger F; Honold J; Hoffmann J; Urbich C; Lehmann R; Arenzana-Seisdesdos F; Aicher A; Heeschen C; Fichtlscherer S; Zeiher AM; Dimmeler S. 2005. Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 97(11):1142-51. [PubMed: 16254213]  [MGI Ref ID J:117515]

Walter DH; Rochwalsky U; Reinhold J; Seeger F; Aicher A; Urbich C; Spyridopoulos I; Chun J; Brinkmann V; Keul P; Levkau B; Zeiher AM; Dimmeler S; Haendeler J. 2007. Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor. Arterioscler Thromb Vasc Biol 27(2):275-82. [PubMed: 17158356]  [MGI Ref ID J:128062]

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 & HusbandryThis strain originated on a B6;129X background and has been backcrossed to C57BL/6 for at least eight generations (2/03). Homozygous mice die perinatally. Coat color expected from breeding:Black

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* $2140.00
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 10 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* $2782.00
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 10 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
   Wild-type from the colony
   000664 C57BL/6J
 
  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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