Loading Mouse GIF
Loading...

Strain Name:
C57BL/6-Relntm1.1Arbo/Mmjax
Stock Number:
071381-JAX
Citation ID:
RRID:MMRRC_071381-JAX
Other Names:
Reelin-COLBOS

Strain Information

Relntm1.1Arbo
Name: reelin; targeted mutation 1.1, Joseph Arboleda-Velasquez
Synonyms: RELN H3448R, mRELN-COLBOS
Type: Allele
Species: Mus musculus
Chromosome: 5
Alteration at locus: Targeted Mutation
Genetic Alterations

Reelin-COLBOS knock-in mice express an H3448R (histidine to arginine) amino acid substitution in the Reln (reelin) locus. The H3448R mutation models the human H3447R variant, and serves as a gain of function mutation that provides resistance to Autosomal dominant Alzheimer's disease (ADAD). This strain may be useful for studies of Alzheimer's disease.

ES Cell Line
C57BL/6N-PRX-B6N #1 derived from C57BL/6N
Phenotype

Reln encodes for the glycoprotein, reelin, that is secreted by specific cell types in the developing brain. Reelin has been implicated in cell-cell interactions to activate neuronal migration and cortical laminar formation.

Reelin-COLBOS (COLBOS – Columbia-Boston biomarker research study) knock-in mice express an H3448R (histidine to arginine) amino acid substitution in the C-terminal of Reln. The mutation corresponds to a rare human H3447R variant found in a male patient with Autosomal dominant Alzheimer’s disease (ADAD). The patient, although carrying the PSEN1-E280A mutation, had a limited entorhinal Tau tangle burden. Mice homozygous for the mutation are viable and fertile, with no overt phenotype. The mutation creates a gain of function hypermorph that has enhanced phosphorylation of Dab1 in homozygous males; activation of DAB1 reduces human Tau phosphorylation. Reelin-COLBOS homozygous males also have a mild increase in cerebellar neurons. When combined with a human tauopathy mouse model (Tg(Prnp-MAPT*P301L)JNPL3Hlmc), males exhibit a significant reduction of Tau phosphorylation in the hippocampus and medulla oblongata, as well as a reduction in the limb-clasping response.

MeSH Terms
  • Animals
  • Female
  • Humans
  • Male
  • Mice
  • Alzheimer Disease/genetics
  • Alzheimer Disease/metabolism
  • Arthrogryposis
  • Heterozygote
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Signal Transduction
Strain Development
This model was generated via homologous recombination as a fee-for-service (Taconic-Cyagen). The targeting vector contained a histidine to arginine amino acid substitution at position 3448 (H3448R; CAC to CGT) inserted into exon 64 in the 3' homology arm of the Reln (reelin) gene on chromosome 5. A neomycin cassette flanked by self-deletion anchor sites was present in the construct. The mutation is orthologous to the human H3447R mutation. The construct was electroporated into C57BL/6N-derived embryonic stem (ES) cells (C57BL/6N-PRX-B6N #1, Cyagen). Correctly targeted ES cells were injected into blastocysts. The resulting male chimeras were crossed to C57BL/6N females The strain has been crossed to C57BL/6J for at least 1 generations by the donating. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
Suggested Control Mice
C57BL/6J
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Models for Human Disease
  • Neurobiology
  • Research Tools
  • Sensorineural
Donor
Joseph Arboleda-velasquez, M.D., Schepens Eye Research Institute, Massachusetts Eye and Ear.
Primary Reference

Lopera F, Marino C, Chandrahas AS, O'Hare M, Villalba-Moreno ND, Aguillon D, Baena A, Sanchez JS, Vila-Castelar C, Ramirez Gomez L, Chmielewska N, Oliveira GM, Littau JL, Hartmann K, Park K, Krasemann S, Glatzel M, Schoemaker D, Gonzalez-Buendia L, Delgado-Tirado S, Arevalo-Alquichire S, Saez-Torres KL, Amarnani D, Kim LA, Mazzarino RC, Gordon H, Bocanegra Y, Villegas A, Gai X, Bootwalla M, Ji J, Shen L, Kosik KS, Su Y, Chen Y, Schultz A, Sperling RA, Johnson K, Reiman EM, Sepulveda-Falla D, Arboleda-Velasquez JF, Quiroz YT. Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man. Nat Med. 2023 May;29(5):1243-1252. doi: 10.1038/s41591-023-02318-3. Epub 2023 May 15. (Medline PMID: 37188781)

Colony and Husbandry Information

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross
Generation
N=2 into C57BL6/J
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
4 to 6
Recommended wean age
4 Weeks
Average Pups Weaned
4 to 6

Order Request Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
071381-JAX-HOM-F
071381-JAX-HOM-M
071381-JAX-HET-F
071381-JAX-HET-M
071381-JAX-WT-F
071381-JAX-WT-M
Homozygous Female
Homozygous Male
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
$229.00 / Non-Profit Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.