Strain Name:

B6;FVB-Nrn1tm1.2Ndiv

Stock Number:

018402

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
These Nrn1 (or cpg15) knock-out mice may have applications in studies examining the roles played by synapse maturation and stabilization on learning ability.

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.FVB-Nrn1tm1.2Ndiv/J    (Changed: 26-JUL-13 )
Type Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating Investigator Elly Nedivi,   Massachusetts Institute of Technology

Description
Cpg15-/- mice lack exons 2-3 of the neuritin 1 (Nrn1) gene, abolishing gene expression. CPG15 is a glycosyl-phosphoinositide (GPI) protein tethered to neural progenitors as well as postmitotic-differentiating neurons of the thalamus and forebrain, including hippocampus and cortex, as well as some brainstem sensory nuclei. CPG15 promotes neurite outgrowth and branching, synapse formation, and activity-dependent plasticity. These Cpg15-/- mice exhibit a delay in axonal and dendritic arborization and maturation of excitatory synapses. Neural progenitors seem unaffected. The development of excitatory synaptic contacts is delayed, leading to eventual dendritic spine loss. These mice also display poor learning with delayed acquisition of new memories. Heterozygous mice are viable and fertile. Homozygotes viable and fertile, 3% smaller, and weigh 20-30% less than wildtype littermates. Some post-natal lethality occurs.

Development
A targeting vector was designed to insert a loxP site upstream of exon 2 and a floxed Frt-flanked neomycin resistance (neo) cassette downstream of exon 3 of the neuritin 1 (Nrn1) gene. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into BALB/c blastocysts. The resulting Cpg15flox-neo/+ offspring were bred to C57BL/6 mice. To remove the neo cassette, fertilized eggs from Cpg15flox-neo/+ mice were transiently transfected with a pOG-Flpe6 expression plasmid resulting in Cpg15flox/+ offspring. These Cpg15flox/+ were then bred with B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) to removed exons 2-3. Cpg15+/- mice were bred together to create Cpg15-/- mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome were segregating, and 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. It has been recently determined that the B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) used in strain development are on a mixed C57BL/6J ; C57BL/6N genetic background. This data also suggests that these mice were not completely backcrossed or contain a contaminating allele.

Control Information

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

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Nrn1tm1.2Ndiv/Nrn1tm1.2Ndiv

        C57BL/6-Nrn1tm1.2Ndiv
  • nervous system phenotype
  • *normal* nervous system phenotype
    • brain weight and gross anatomy are similar to wild-type littermates at 8 weeks of age   (MGI Ref ID J:178970)
    • abnormal dendrite morphology
      • at P15 dentate gyrus granule cells have significantly fewer branch tips per neuron   (MGI Ref ID J:178970)
      • between P 15 and P60 branch tip pruning in dentate gyrus granule cells is less pronounce compared to wild-type controls   (MGI Ref ID J:178970)
      • by 2 months of age dendritic arbors of dentate gyrus granule cells appear similar to wild-type controls   (MGI Ref ID J:178970)
    • abnormal miniature excitatory postsynaptic currents
      • at P7 in the dentate gyrus mEPSCs occur with lower frequency and have reduced amplitudes indicating a delay in synapse development and maturation   (MGI Ref ID J:178970)
      • however, at 2 months of age amplitudes are similar to controls   (MGI Ref ID J:178970)
    • abnormal nervous system development
      • neuropil development is initially delayed but eventually reaches wild-type levels   (MGI Ref ID J:178970)
      • abnormal CNS synapse formation
        • fewer synapses are formed but those formed are less likely to be pruned resulting in similar synapse numbers to wild-type controls at 9 months of age   (MGI Ref ID J:178970)
        • delayed CNS synapse formation
          • at P7 in the dentate gyrus mEPSCs occur with lower frequency and have reduced amplitudes indicating a delay in synapse development and maturation   (MGI Ref ID J:178970)
          • however, at 2 months of age amplitudes are similar to wild-type controls   (MGI Ref ID J:178970)
      • delayed axon extension
        • delay in outgrowth of retinal ganglion cell axons into the lateral geniculate nucleus such that the retinogeniculate projection area is reduced at P9 but catches up to wild-type by P90   (MGI Ref ID J:178970)
    • abnormal synapse morphology
      • at 2 months of age in the dentate gyrus, but not in the hippocampal CA1 region, the density of asymmetric synapses on dendritic spines is reduced   (MGI Ref ID J:178970)
      • at 2 months of age post-synaptic density lengths are increased by 33% compared to wild-type controls in the in the dentate gyrus, but not in the hippocampal CA1 region   (MGI Ref ID J:178970)
  • growth/size/body phenotype
  • decreased body length
    • 3% shorter in length   (MGI Ref ID J:178970)
  • decreased body weight
    • weigh on average 20-30% less than wild-type littermates   (MGI Ref ID J:178970)
  • behavior/neurological phenotype
  • abnormal spatial learning
    • slower acquisition of the task in a Morris water maze assay   (MGI Ref ID J:178970)
  • impaired contextual conditioning behavior
    • display less freezing in response to context both 1 h and 24 h after training   (MGI Ref ID J:178970)
  • impaired cued conditioning behavior
    • display less freezing in response to the tone cue   (MGI Ref ID J:178970)
    • display less freezing in response to context both 1 h and 24 h after training   (MGI Ref ID J:178970)
  • cellular phenotype
  • delayed axon extension
    • delay in outgrowth of retinal ganglion cell axons into the lateral geniculate nucleus such that the retinogeniculate projection area is reduced at P9 but catches up to wild-type by P90   (MGI Ref ID J:178970)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Neurodevelopmental Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nrn1tm1.2Ndiv
Allele Name targeted mutation 1.2, Elly Nedivi
Allele Type Targeted (Null/Knockout)
Mutation Made By Elly Nedivi,   Massachusetts Institute of Technology
Strain of OriginC57BL/6
Gene Symbol and Name Nrn1, neuritin 1
Chromosome 13
Gene Common Name(s) 0710008J23Rik; NRN; RIKEN cDNA 0710008J23 gene; cpg15; dJ380B8.2;
Molecular Note A loxP site was inserted upstream of exon 2 and a loxP and FRT flanked neo cassette was inserted downstream of exon 3 via homologous recombination. Recombinase mediated recombination removed the neo cassette and exons 2 and 3. [MGI Ref ID J:178970]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Cre Melt Curve Analysis,

MELT


Generic Cre Melt Curve Analysis,

Probe


Nrn1tm1.2Ndiv,

Separated MCA


Nrn1tm1.2Ndiv, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fujino T; Leslie JH; Eavri R; Chen JL; Lin WC; Flanders GH; Borok E; Horvath TL; Nedivi E. 2011. CPG15 regulates synapse stability in the developing and adult brain. Genes Dev 25(24):2674-85. [PubMed: 22190461]  [MGI Ref ID J:178970]

Additional References

Nrn1tm1.2Ndiv related

Picard N; Leslie JH; Trowbridge SK; Subramanian J; Nedivi E; Fagiolini M. 2014. Aberrant development and plasticity of excitatory visual cortical networks in the absence of cpg15. J Neurosci 34(10):3517-22. [PubMed: 24599452]  [MGI Ref ID J:209345]

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, heterozygous mice may be bred together. Homozygous mice are viable and fertile, but the DI reports some post-natal lethality suggesting the Homs that survive have the mildest phenotype. They breed Het x Het to keep from attenuating the phenotype.

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 (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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