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. Species laboratory mouse   Donating Investigator Dr. 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-17~92^delta) 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

Mirc1^tm1.2Tyj/Mirc1⁺

        involves: 129S4/SvJae * C57BL/6 * FVB/N * SJL

• growth/size phenotype
• decreased body size
  • newborn mice are slightly smaller than wild-type littermates   (MGI Ref ID J:134861)

Mirc1^tm1.2Tyj/Mirc1^tm1.2Tyj

        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 Mirn17-92^tm1.3Tyj 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 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)
• 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
• 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)

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

Mirc1^tm1.2Tyj/Mirc1⁺

        involves: 129S4/SvJae * C57BL/6

• growth/size 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)

Mirc1^tm1.2Tyj/Mirc1^tm1.2Tyj

        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 Name		v6.5
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

Mirn17-92^tm1.2Tyj, 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

Mirc1^tm1.2Tyj related

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; 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 & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygotes are perinatal lethal.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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