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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator IMR Colony,   The Jackson Laboratory

Description
These mice possess loxP sites on either side of exons 2 and 3 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele.

For example, when crossed to a strain expressing Cre recombinase in neuronal and glial cell precursors (see Stock No. 003771), this mutant mouse strain may be useful in studies of neurogenesis.

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. 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 loxP site flanked targeting vector containing a neomycin resistance gene under the control of the phosphoglycerate kinase, PGK, promoter was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 3 of the targeted gene, and another loxP site was inserted upstream of exon 2. This construct was electroporated into 129 derived embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, then crossed to another mutant strain. The other mutant allele was subsequently bred out of the line. These mice carry only the conditional floxed mutant allele and arrived on a mixed B6;129 background (as Stock No. 006933). Mice from that colony were then backcrossed to C57BL/6J for multiple generations to generate this congenic strain (Stock No. 007003).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Mycn^tm1Psk allele

006933

B6;129-Mycntm1Psk/J

View Strains carrying   Mycn^tm1Psk     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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.

Mycn^tm1Psk/Mycn^tm1Psk Tg(Nes-cre)1Kln/0

        involves: 129 * C57BL/6 * SJL   (conditional)

• growth/size phenotype
• postnatal growth retardation
  • moderate growth retardation   (MGI Ref ID J:79489)
• nervous system phenotype
• *normal* nervous system phenotype
  • neuronal precursor cell apoptosis is similar to controls   (MGI Ref ID J:79489)
• • abnormal cerebellum morphology
    • cerebellum appears disorganized   (MGI Ref ID J:79489)
    • at P20 in the rostral region all 3 layers are severely affected   (MGI Ref ID J:79489)
  • • abnormal cerebellar Purkinje cell layer
      • disrupted   (MGI Ref ID J:79489)
    • • decreased Purkinje cell number   (MGI Ref ID J:79489)
      • ectopic Purkinje cell   (MGI Ref ID J:79489)
    • abnormal cerebellar granule layer
      • granule cell density is reduced 3- to 6-fold   (MGI Ref ID J:79489)
      • at P20 total granule cell numbers are reduced about 30-fold   (MGI Ref ID J:79489)
    • abnormal cerebellar molecular layer
      • fails to expand resulting in decreased area and decreased cell number   (MGI Ref ID J:79489)
    • abnormal cerebellum development
      • profound reduction in the progenitor cell pool in both the external granule cell layer and in the neuroepithelium   (MGI Ref ID J:79489)
      • at E12.5 a significant reduction in neuroprogenitor cell numbers is seen in the cerebellar neuroepithelium and rhombic lip and the interior differentiating zone is reduced in size   (MGI Ref ID J:79489)
      • at E17.5 a subset of rhombic lip neuroprogenitor cells are more rounded and more densely packed   (MGI Ref ID J:79489)
    • • abnormal cerebellar foliation
        • severe defects in foliation   (MGI Ref ID J:79489)
      • abnormal cerebellum external granule cell layer morphology
        • profound reduction in the progenitor cell pool   (MGI Ref ID J:79489)
        • decrease is more pronounced in the rostral region   (MGI Ref ID J:79489)
        • the most rostral portion of the EGL is absent   (MGI Ref ID J:79489)
    • small cerebellum
      • the developing cerebellum is particularly small   (MGI Ref ID J:79489)
      • at P20 the absolute weight and percent of total brain weight of the cerebellum is reduced by 4- to 6-fold compared to controls   (MGI Ref ID J:79489)
  • abnormal cerebral cortex morphology
    • the developing cerebral cortex is particularly small   (MGI Ref ID J:79489)
  • abnormal cortical ventricular zone morphology
    • many regions of the VZ are noticeably reduced in thickness   (MGI Ref ID J:79489)
    • at E17.5 in the lateral VZ neuroprogenitor cells are more rounded and more densely packed   (MGI Ref ID J:79489)
  • abnormal embryonic neuroepithelium morphology
    • the cerebellar neuroepithelium appears thinner, displays breaks, and has a deficiency in progenitor cells   (MGI Ref ID J:79489)
  • abnormal neuron differentiation
    • progenitor cells display smaller nuclei   (MGI Ref ID J:79489)
  • • decreased neuronal precursor cell number
      • in the cerebellar neuroepithelium, rhombic lip, and external granule cell layer at E12.5 and E17.5   (MGI Ref ID J:79489)
    • premature neuronal precursor differentiation
      • premature differentiation is seen both in vivo and in vitro   (MGI Ref ID J:79489)
  • abnormal neuronal precursor proliferation
    • striking reduction in proliferation in the central nervous system in general at E13   (MGI Ref ID J:79489)
    • only a very small fraction of cells in the interior of the cerebellum primordium are proliferating at E13   (MGI Ref ID J:79489)
    • significant decrease in the number of proliferating cells in the ventricular zone of the telencephalon at E13   (MGI Ref ID J:79489)
  • decreased brain size
    • at 8 - 16 weeks of age mice display profound microencephaly   (MGI Ref ID J:79489)
    • decrease in brain size can be detected at E12.5   (MGI Ref ID J:79489)
    • total brain mass relative to total body weight is reduced 2 fold compared to controls   (MGI Ref ID J:79489)
• craniofacial phenotype
• microcephaly
  • decrease in head size can be detected at E12.5   (MGI Ref ID J:79489)
• vision/eye phenotype
• microphthalmia   (MGI Ref ID J:79489)
• embryogenesis phenotype
• abnormal embryonic neuroepithelium morphology
  • the cerebellar neuroepithelium appears thinner, displays breaks, and has a deficiency in progenitor cells   (MGI Ref ID J:79489)
• cellular phenotype
• abnormal neuron differentiation
  • progenitor cells display smaller nuclei   (MGI Ref ID J:79489)
• • decreased neuronal precursor cell number
    • in the cerebellar neuroepithelium, rhombic lip, and external granule cell layer at E12.5 and E17.5   (MGI Ref ID J:79489)
  • premature neuronal precursor differentiation
    • premature differentiation is seen both in vivo and in vitro   (MGI Ref ID J:79489)
• abnormal neuronal precursor proliferation
  • striking reduction in proliferation in the central nervous system in general at E13   (MGI Ref ID J:79489)
  • only a very small fraction of cells in the interior of the cerebellum primordium are proliferating at E13   (MGI Ref ID J:79489)
  • significant decrease in the number of proliferating cells in the ventricular zone of the telencephalon at E13   (MGI Ref ID J:79489)

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		Mycntm1Psk
Allele Name		targeted mutation 1, Paul S Knoepfler
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Mycnloxp; Mycntm1Rne; N-mycFL; NmycFl;
Mutation Made By		Paul Knoepfler,   UC Davis Genome Center
Strain of Origin		129
Gene Symbol and Name		Mycn, v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)
Chromosome		12
Gene Common Name(s)		MODED; N-myc; NMYC; Nmuc1; Nmyc-1; Nmyc1; ODED; bHLHe37; neuroblastoma myc-related oncogene 1;
Molecular Note		Sequence encompassing exons 2 and 3 was flanked by a single loxP site upstream and a floxed neo cassette downstream. RT-PCR analysis revealed a 25% to 30% reduction in the amount of transcript in homozygous mutant mice. [MGI Ref ID J:79489]

Genotyping

Genotyping Information

Genotyping Protocols

Mycn^tm1Psk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Knoepfler PS; Cheng PF; Eisenman RN. 2002. N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16(20):2699-712. [PubMed: 12381668]  [MGI Ref ID J:79489]

Additional References

Mycn^tm1Psk related

Chen Q; Khoury M; Chen J. 2009. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci U S A :. [PubMed: 19966223]  [MGI Ref ID J:155817]

Dominguez-Frutos E; Lopez-Hernandez I; Vendrell V; Neves J; Gallozzi M; Gutsche K; Quintana L; Sharpe J; Knoepfler PS; Eisenman RN; Trumpp A; Giraldez F; Schimmang T. 2011. N-myc controls proliferation, morphogenesis, and patterning of the inner ear. J Neurosci 31(19):7178-89. [PubMed: 21562282]  [MGI Ref ID J:173398]

Habib T; Park H; Tsang M; de Alboran IM; Nicks A; Wilson L; Knoepfler PS; Andrews S; Rawlings DJ; Eisenman RN; Iritani BM. 2007. Myc stimulates B lymphocyte differentiation and amplifies calcium signaling. J Cell Biol 179(4):717-31. [PubMed: 17998397]  [MGI Ref ID J:135554]

Harmelink C; Peng Y; DeBenedittis P; Chen H; Shou W; Jiao K. 2013. Myocardial Mycn is essential for mouse ventricular wall morphogenesis. Dev Biol 373(1):53-63. [PubMed: 23063798]  [MGI Ref ID J:190992]

Hatton BA; Knoepfler PS; Kenney AM; Rowitch DH; de Alboran IM; Olson JM; Eisenman RN. 2006. N-myc Is an Essential Downstream Effector of Shh Signaling during both Normal and Neoplastic Cerebellar Growth. Cancer Res 66(17):8655-61. [PubMed: 16951180]  [MGI Ref ID J:112411]

Heine VM; Priller M; Ling J; Rowitch DH; Schuller U. 2010. Dexamethasone destabilizes Nmyc to inhibit the growth of hedgehog-associated medulloblastoma. Cancer Res 70(13):5220-5. [PubMed: 20530674]  [MGI Ref ID J:161601]

Kopecky BJ; Decook R; Fritzsch B. 2012. N-Myc and L-Myc are essential for hair cell formation but not maintenance. Brain Res 1484:1-14. [PubMed: 23022312]  [MGI Ref ID J:193566]

Kopecky BJ; Jahan I; Fritzsch B. 2013. Correct Timing of Proliferation and Differentiation is Necessary for Normal Inner Ear Development and Auditory Hair Cell Viability. Dev Dyn 242(2):132-47. [PubMed: 23193000]  [MGI Ref ID J:191198]

Kuwahara A; Hirabayashi Y; Knoepfler PS; Taketo MM; Sakai J; Kodama T; Gotoh Y. 2010. Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex. Development 137(7):1035-44. [PubMed: 20215343]  [MGI Ref ID J:158681]

Laurenti E; Varnum-Finney B; Wilson A; Ferrero I; Blanco-Bose WE; Ehninger A; Knoepfler PS; Cheng PF; MacDonald HR; Eisenman RN; Bernstein ID; Trumpp A. 2008. Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 3(6):611-24. [PubMed: 19041778]  [MGI Ref ID J:149864]

Martins RA; Zindy F; Donovan S; Zhang J; Pounds S; Wey A; Knoepfler PS; Eisenman RN; Roussel MF; Dyer MA. 2008. N-myc coordinates retinal growth with eye size during mouse development. Genes Dev 22(2):179-93. [PubMed: 18198336]  [MGI Ref ID J:131387]

Okubo T; Knoepfler PS; Eisenman RN; Hogan BL. 2005. Nmyc plays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation. Development 132(6):1363-74. [PubMed: 15716345]  [MGI Ref ID J:97215]

Smith KN; Singh AM; Dalton S. 2010. Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 7(3):343-54. [PubMed: 20804970]  [MGI Ref ID J:164438]

Zindy F; Knoepfler PS; Xie S; Sherr CJ; Eisenman RN; Roussel MF. 2006. N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci U S A 103(31):11579-83. [PubMed: 16864777]  [MGI Ref ID J:111800]

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	Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining a live congenic colony, these mice may be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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