Strain Name:

STOCK Mirc1tm1.2Tyj/J

Stock Number:

008459

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The miR-17~92 (microRNA17-92) cluster, overexpressed in human cancers, is deleted in this targeted mutant strain. Mice homozygous for this null allele (miR-17~92delta) die perinatally, displaying cardiac defects and hypoplastic lungs. In fetal liver reconstitution experiments, a defect in B-cell development (partial block at the pro-B to pre-B transition) is observed. This strain may be useful in studying the link between the region's oncogenic properties and its functions during B cell lymphopoiesis and lung development.

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 STOCK Mir17-92tm1.2Tyj/J    (Changed: 21-JUL-11 )
B6;129S4-Mirn17-92tm1.1Tyj/J    (Changed: 07-JUL-08 )
B6;Cg-Mirn17-Mirn92tm1.1Tyj/J    (Changed: 26-JUN-08 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Tyler Jacks,   Massachusetts Institute of Technology

Description
The miR-17~92 (Mir17, Mir18, Mir19a, Mir20a, Mir19b-1, Mir92-1) cluster, overexpressed in human cancers, is deleted in this targeted mutant strain. Heterozygous mice are viable and fertile. Mice homozygous for this null allele (miR-17~92delta) die perinatally, displaying cardiac defects and hypoplastic lungs. In fetal liver reconstitution experiments, a defect in B-cell development (partial block at the pro-B to pre-B transition) is observed. This strain may be useful in studying the link between the region's oncogenic properties and its functions during B cell lymphopoiesis and lung development.

Development
loxP sites were introduced 5' of the Mirn17 gene and 3' of the Mirn92-1 gene. The floxed region was followed by an Frt-flanked neomycin cassette. The targeting vector was introduced to V6.5 (C57BL/6 x 129S4/SvJae)F1-derived embryonic stem (ES) cells. The neomycin cassette was removed through Flp-mediated excision via a C57BL/6 background strain. Crosses with a C57BL/6 background Cre deleter strain (human ACTB beta actin promoter) excised the floxed genes. This strain was maintained on a mixed C57BL/6 and 129S4 background by the donating laboratory.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mirc1
008458   STOCK Mirc1tm1.1Tyj/J
View Strains carrying other alleles of Mirc1     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Feingold Syndrome 2; FGLDS2
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Mirc1tm1.2Tyj/Mirc1+

        involves: 129S4/SvJae * C57BL/6 * FVB/N * SJL
  • growth/size/body phenotype
  • decreased body size
    • newborn mice are slightly smaller than wild-type littermates   (MGI Ref ID J:134861)

Mirc1tm1.2Tyj/Mirc1tm1.2Tyj

        involves: 129S4/SvJae * C57BL/6 * FVB/N * SJL
  • mortality/aging
  • complete neonatal lethality
    • no viable homozygotes are produced from heterozygous intercrosses; homozygous phenotype is indistinguishable from Mirn17-92tm1.3Tyj homozygotes   (MGI Ref ID J:134861)
  • embryogenesis phenotype
  • decreased embryo size
    • at E13.5, mutants can be distinguished by their smaller size   (MGI Ref ID J:134861)
    • decreased embryo weight
      • by E18.5, mutant weights are 60% of wild-type littermates   (MGI Ref ID J:134861)
  • growth/size/body phenotype
  • decreased embryo size
    • at E13.5, mutants can be distinguished by their smaller size   (MGI Ref ID J:134861)
    • decreased embryo weight
      • by E18.5, mutant weights are 60% of wild-type littermates   (MGI Ref ID J:134861)
  • cardiovascular system phenotype
  • abnormal interventricular septum morphology   (MGI Ref ID J:134861)
  • respiratory system phenotype
  • pulmonary hypoplasia
    • E18.5-P0 animals have severely hypoplastic lungs but histological examination does not reveal any branching defect or other developmental abnormalities   (MGI Ref ID J:134861)
  • hematopoietic system phenotype
  • abnormal B cell differentiation
    • lethally irradiated mice transplanted with E14.5 mutant liver cells are found to have reduced percentages of pre-B cells and cells of later stages   (MGI Ref ID J:134861)
    • decreased pre-B cell number
      • fetal livers (E18.5) show a greatly reduced percentage and absolute number of pre-B cells   (MGI Ref ID J:134861)
  • increased B cell apoptosis
    • mutant fetal livers display increased apoptosis specific to the B cell compartment without higher levels in non-B cells   (MGI Ref ID J:134861)
    • higher levels of apoptosis are not observed in other organs   (MGI Ref ID J:134861)
  • immune system phenotype
  • abnormal B cell differentiation
    • lethally irradiated mice transplanted with E14.5 mutant liver cells are found to have reduced percentages of pre-B cells and cells of later stages   (MGI Ref ID J:134861)
    • decreased pre-B cell number
      • fetal livers (E18.5) show a greatly reduced percentage and absolute number of pre-B cells   (MGI Ref ID J:134861)
  • increased B cell apoptosis
    • mutant fetal livers display increased apoptosis specific to the B cell compartment without higher levels in non-B cells   (MGI Ref ID J:134861)
    • higher levels of apoptosis are not observed in other organs   (MGI Ref ID J:134861)
  • cellular phenotype
  • increased B cell apoptosis
    • mutant fetal livers display increased apoptosis specific to the B cell compartment without higher levels in non-B cells   (MGI Ref ID J:134861)
    • higher levels of apoptosis are not observed in other organs   (MGI Ref ID J:134861)

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

Mirc1tm1.2Tyj/Mirc1+

        involves: 129S4/SvJae * C57BL/6
  • growth/size/body phenotype
  • decreased body size   (MGI Ref ID J:188762)
  • craniofacial phenotype
  • microcephaly
    • the anterior-posterior axis of the skull is shortened and the skull shows an overall reduction in size   (MGI Ref ID J:188762)
  • limbs/digits/tail phenotype
  • brachyphalangia
    • mesophalanx of the fifth finger is shorter   (MGI Ref ID J:188762)
    • however, other long bones in the hands are only marginally shorter than in wild-type and syndactyly is not observed   (MGI Ref ID J:188762)
  • skeleton phenotype
  • brachyphalangia
    • mesophalanx of the fifth finger is shorter   (MGI Ref ID J:188762)
    • however, other long bones in the hands are only marginally shorter than in wild-type and syndactyly is not observed   (MGI Ref ID J:188762)

Mirc1tm1.2Tyj/Mirc1tm1.2Tyj

        involves: 129S4/SvJae * C57BL/6
  • cardiovascular system phenotype
  • decreased heart right ventricle size   (MGI Ref ID J:169047)
  • double outlet right ventricle   (MGI Ref ID J:169047)
  • ventricular septal defect   (MGI Ref ID J:169047)
  • craniofacial phenotype
  • microcephaly
    • seen in all E18.5 mutants   (MGI Ref ID J:188762)
  • limbs/digits/tail phenotype
  • abnormal forelimb zeugopod morphology
    • E18.5 mutants exhibit dysmorphic zeugopods   (MGI Ref ID J:188762)
  • abnormal hindlimb zeugopod morphology
    • E18.5 mutants exhibit dysmorphic zeugopods   (MGI Ref ID J:188762)
  • abnormal phalanx morphology
    • complete absence of the mesophalanx of the fifth digit is seen in E18.5 mutants   (MGI Ref ID J:188762)
    • brachyphalangia
      • E18.5 mutants exhibit the presence of a small mesophalanx of the second digit and hypoplasia of the first digital ray   (MGI Ref ID J:188762)
  • fused carpal bones
    • E18.5 mutants exhibit fusion of the proximal carpal bones   (MGI Ref ID J:188762)
  • skeleton phenotype
  • abnormal phalanx morphology
    • complete absence of the mesophalanx of the fifth digit is seen in E18.5 mutants   (MGI Ref ID J:188762)
    • brachyphalangia
      • E18.5 mutants exhibit the presence of a small mesophalanx of the second digit and hypoplasia of the first digital ray   (MGI Ref ID J:188762)
  • cervical vertebral fusion
    • all E18.5 mutants exhibit fusion of the cervical vertebrae   (MGI Ref ID J:188762)
  • delayed endochondral bone ossification
    • E18.5 mutants exhibit a severe and general delay of endochondral ossification   (MGI Ref ID J:188762)
  • delayed intramembranous bone ossification
    • E18.5 mutants exhibit a severe and general delay of membranous ossification, with delayed ossification of occipital, parietal and frontal bones   (MGI Ref ID J:188762)
  • fused carpal bones
    • E18.5 mutants exhibit fusion of the proximal carpal bones   (MGI Ref ID J:188762)
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      heart
      lung
Postnatal Lethality
      Homozygous

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mirc1tm1.2Tyj
Allele Name targeted mutation 1.2, Tyler Jacks
Allele Type Targeted (knock-out)
Common Name(s) Mirn17-92tm1.2Tyj; miR-17~92delta;
Strain of Origin(C57BL/6 x 129S4/SvJae)F1
ES Cell Line Namev6.5
ES Cell Line Strain(C57BL/6 x 129S4/SvJae)F1
Gene Symbol and Name Mirc1, microRNA cluster 1, including Mir17 through Mir92-1
Chromosome 14
Gene Common Name(s) Mir17-92; Mirn17-92; miR-17-92; miR-17~92; microRNA cluster 17-92;
Molecular Note Crossing Mirc1tm1.1Tyj mice to a Cre deleter strain (human ACTB beta actin promoter) excised the floxed cluster, including Mir17, Mir18a, Mir19a, Mir20a, Mir19b-1, and Mir92-1. This results in a null allele. [MGI Ref ID J:134861]

Genotyping

Genotyping Information

Genotyping Protocols

Mirn17-92tm1.2Tyj, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ventura A; Young AG; Winslow MM; Lintault L; Meissner A; Erkeland SJ; Newman J; Bronson RT; Crowley D; Stone JR; Jaenisch R; Sharp PA; Jacks T. 2008. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132(5):875-86. [PubMed: 18329372]  [MGI Ref ID J:134861]

Additional References

Mirc1tm1.2Tyj related

Bai Y; Wang J; Morikawa Y; Bonilla-Claudio M; Klysik E; Martin JF. 2013. Bmp signaling represses Vegfa to promote outflow tract cushion development. Development 140(16):3395-402. [PubMed: 23863481]  [MGI Ref ID J:199300]

Chen JA; Huang YP; Mazzoni EO; Tan GC; Zavadil J; Wichterle H. 2011. Mir-17-3p controls spinal neural progenitor patterning by regulating Olig2/Irx3 cross-repressive loop. Neuron 69(4):721-35. [PubMed: 21338882]  [MGI Ref ID J:174745]

Wang J; Bai Y; Li H; Greene SB; Klysik E; Yu W; Schwartz RJ; Williams TJ; Martin JF. 2013. MicroRNA-17-92, a direct Ap-2alpha transcriptional target, modulates T-box factor activity in orofacial clefting. PLoS Genet 9(9):e1003785. [PubMed: 24068957]  [MGI Ref ID J:202467]

Wang J; Greene SB; Bonilla-Claudio M; Tao Y; Zhang J; Bai Y; Huang Z; Black BL; Wang F; Martin JF. 2010. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell 19(6):903-12. [PubMed: 21145505]  [MGI Ref ID J:169047]

Yu Z; Baserga R; Chen L; Wang C; Lisanti MP; Pestell RG. 2010. microRNA, cell cycle, and human breast cancer. Am J Pathol 176(3):1058-64. [PubMed: 20075198]  [MGI Ref ID J:158380]

de Pontual L; Yao E; Callier P; Faivre L; Drouin V; Cariou S; Van Haeringen A; Genevieve D; Goldenberg A; Oufadem M; Manouvrier S; Munnich A; Vidigal JA; Vekemans M; Lyonnet S; Henrion-Caude A; Ventura A; Amiel J. 2011. Germline deletion of the miR-17 approximately 92 cluster causes skeletal and growth defects in humans. Nat Genet 43(10):1026-30. [PubMed: 21892160]  [MGI Ref ID J:188762]

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 maintained as a live colony, heterozygotes may be bred. Homozygotes are perinatal lethal.

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* $2450.00
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* $3185.00
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).

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
 
  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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