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Strain Name:
C57BL/6J-Dync1h1em1Shzb/Mmjax
Stock Number:
076078-JAX
Citation ID:
RRID:MMRRC_076078-JAX
Other Names:
DYNC1H1 P3018S heterozygous (HET) knockin mouse (c9052C > T(P3018S)

Strain Information

QUALITY CONTROL OF C57BL/6J-Dync1h1em1Shzb/Mmjax  |  The Jackson Laboratory
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distributionn.d.
Fecundity/breeding performancen.d.

1 When indicated as verified ("YES"), then please note that information presented is to the best of our knowledge correct and up-to-date at the time of verification at the MMRRC Distribution Center; however, this information is subject to change due to breeding, maintenance, and other actions on the mouse strain at the MMRRC Distribution Center; direct any questions on this table to the MMRRC Distribution Center for this mouse stain.

2 If verification has not been performed (as indicated by "NO"), investigators may request specific verification testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Dync1h1em1Shzb
Name: dynein cytoplasmic 1 heavy chain 1; endonuclease-mediated mutation 1, Bridget Shafit-Zagardo
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 12
Alteration at locus: CRISPR
Dync1h1
Name: dynein cytoplasmic 1 heavy chain 1
Synonyms: MAP1C, dynein heavy chain, retrograde transport, Dnec1, Loa, 9930018I23Rik, Dnchc1, Swl
Type: Gene
Species: Mouse
Chromosome: 12
NCBI: 13424
HGNC: HGNC:2961
Homologene: 1053
Genetic Alterations
Using CRIPSR/Cas9 mediated genome editing, a point mutation c9052C > T in the Dync1h1 gene was generated. This mutation is a patient-specific de novo point mutation found within the third functional ATPase domain.
ES Cell Line
Not Applicable
Phenotype

Cytoplasmic dynein heavy chain (Dync1h1) is a is a microtubule motor protein responsible for retrograde intracellular transport. A mouse model was generated carrying a patient-derived, de novo heterozygous Dync1h1 point mutation in a functional ATPase domain (c.9052C>T; p.P3018S), originally identified in a child with motor deficits and intellectual disability.

  • Heterozygous knock-in mice are viable
    • Hets display increased metabolic rate and locomotor activity, reduced body fat, and motor coordination deficitsm including impaired performance on elevated balance beam and negative geotaxis assays.
  • Homozygous mice are lethal

Immunofluorescent analyses shows abnormal neuronal migration in the dorsal and lateral neocortex with heterotopia in layer I. Neuron-subtype specific transcription factors CUX1 and CTGF identified neurons from layers II/III and VI respectively in cortical layer I, and abnormal pyramidal neurons with MAP2+ dendrites projecting downward from the pial surface.

MeSH Terms
  • Animals
  • Cytoplasmic Dyneins/genetics
  • Cytoplasmic Dyneins/metabolism
  • Mice
  • Mutation/genetics
  • Humans
  • Brain/metabolism
  • Brain/pathology
  • Disease Models, Animal
  • Mice, Transgenic
  • Male
  • Intellectual Disability/genetics
  • Neurons/metabolism
  • Neurons/pathology
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Cell Biology
  • Developmental Biology
  • Metabolism
  • Models for Human Disease
  • Neurobiology
  • Sensorineural
Submitter
Bridget Shafit-zagardo, Ph.D., Albert Einstein Coll Med.
Primary Reference

Ramos RL, De Heredia MMB, Zhang Y, Stout RF, Tindi JO, Wu L, Schwartz GJ, Botbol YM, Sidoli S, Poojari A, Rakowski-Anderson T, Shafit-Zagardo B. Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits. Neurobiol Dis. 2024 Sep;199:106594. doi: 10.1016/j.nbd.2024.106594. Epub 2024 Jul 16. (Medline PMID: 39025270)

Strain Development
The knock-in heterozygous mice with point mutation, c9052C > T in the Dync1h1 gene, were generated on a C57BL/6J background. The Dync1h1 mouse model was constructed using CRIPSR/Cas9 mediated genome editing. Two guide RNAs (gRNAs) targeting introns 46 and 47 of the mouse Dync1h1 gene, a single stranded homology directed repair donor DNA carrying the desired Dync1h1 mutation, and Cas9 protein was injected into the fertilized eggs of C57BL/6J mice. Then the injected fertilized eggs were transferred to the pseudopregnant CD1 female mice for producing pups. The resulting progeny were screened by DNA sequencing to identify correctly targeted founder (F0), F1, and F2 mice. DNA sequencing confirmed that the mice are heterozygous for the point mutation. The mutation was confirmed by DNA sequencing.

Dync1h1 heterozygous (HET) mice are viable and were crossed with both male or female heterozygous and WT mice (C57BL/6J) to obtain heterozygous and wild-type littermates. No homozygous pups have been born over the 2 years of HET x HET matings.


Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.

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
>20
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 4 to 6 months Undetermined
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

Order 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.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Office of Biotechnology and Business Development.

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.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Office of Biotechnology and Business Development

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
076078-JAX-HET-F
076078-JAX-HET-M
076078-JAX-WT-F
076078-JAX-WT-M
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
$200.00 / $200.00
Non-Profit / For-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.