Loading...

Strain Detail Sheet

Published: 09/19/2025
Revised: 09/19/2025

Strain Name:
C57BL/6NJ-Tbr1em2Boro/Mmucd
Stock Number:
075893-UCD
Citation ID:
RRID:MMRRC_075893-UCD
Other Names:
Tbr1K228E

Strain Information

Strain Quality Control

QUALITY CONTROL OF C57BL/6NJ-Tbr1em2Boro/Mmucd  |  University of California at Davis
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3YES
Genetic backgroundn.d.
Viability of genotypes available for distributionYES
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 distribution n.d.
Fecundity/breeding performance n.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.

Gene Details

Tbr1em2Boro
Name: T-box brain transcription factor 1; endonuclease-mediated mutation 2, Brian Oroak
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 2
Alteration at locus: CRISPR
Tbr1
Name: T-box brain transcription factor 1
Synonyms: T-box brain gene 1
Type: Gene
Species: Mouse
Chromosome: 2
Alteration at locus: CRISPR
NCBI: 21375
Homologene: 4807

Additional Resources
IMPC
Google
Entrez
PubMed
IMSR
Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
Genetic Alterations
Lysine codon 228 (AAA) in exon 1 was changed to glutamic acid (GAA) (c.682A>G p.K228E) using an sgRNA and an ssODN template with CRISPR/cas9 technology. p.K228E was identified in a patient with autism.
ES Cell Line
Not applicable

Strain Description

Phenotype
TBR1 is a potential "master regulator" of autism risk by virtue of its direct regulation of an autism-associated gene network in human midfetal brain (Willsey et al., 2013; Notwell et al., 2016).

Tbr1em2Boro (Tbr1K228E) show normal growth and body/brain mass, and normal motor coordination (negative geotaxis) during early postnatal time points.

Tbr1K228E mice exhibit elevated Tbr1 protein levels due to transcriptional upregulation:
  • Heterozygous mice:
    • show 2x Tbr1 protein levels compared to wild-type mice
    • lack the posterior limb of the anterior commissure (AC)
  • Homozygous mice:
    • show 5x the Tbr1 protein levels compared to wild-type mice
    • show ectopic expression of Tbr1 protein across all cortical layers
    • show more severe defects—absence of AC, misdirected callosal fibers, abnormal organization of internal capsule axons, perinatal lethality, and small olfactory bulbs
    • do not show a significant increase on cortical apoptosis (unlike KO mice)
MeSH Terms
  • Animals
  • Axons/metabolism
  • DNA-Binding Proteins/genetics
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Mutation
  • Neurogenesis/genetics
  • T-Box Domain Proteins/genetics
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.

Research Applications

As TBR1 Syndrome is a rare genetic form of autism and intellectual disability, TBR1 is a potential “master regulator” of autism risk by virtue of its direct regulation of an autism-associated gene network in human midfetal brain (Willsey et al., 2013; Notwell et al., 2016).

This strain belongs to the unique allelic series which encompass three major classes of TBR1 clinical variants and a hypomorphic Tbr1 allele:


Variant TypeDescriptionMMRRC ID
Early-truncating frameshiftleads to loss-of-function via nonsense-mediated decay (NMD)

MMRRC: 75892

Missenseclustered in the T-box DNA-binding domain

MMRRC: 75893 (This strain)

Late-truncating frameshift
  • escape NMD and alter the C-terminal domain
  • lead to more severe clinical outcomes (nonverbal, non-mobile)
    • (tbr1syndrome.com; Nambot et al., 2020)
  • are further sub-classified based on the new reading frame generated (ORF1, ORF2)

ORF1: MMRRC: 75894

ORF1: MMRRC: 75895

ORF2: MMRRC: 75898

In-frame indelis an in-frame indel within the C-terminus that may prove useful for domain function studies

MMRRC: 75899

Strain Origin

Donor
Brian O'Roak, Ph.D., Oregon Health and Science University.
Primary Reference

Co M, Barnard RA, Jahncke JN, Grindstaff S, Fedorov LM, Adey AC, Wright KM, O'Roak BJ. Shared and Distinct Functional Effects of Patient-Specific Tbr1 Mutations on Cortical Development. J Neurosci. 2022 Sep 14;42(37):7166-7181. doi: 10.1523/JNEUROSCI.0409-22.2022. Epub 2022 Aug 9. (Medline PMID: 35944998)

Strain Development
CRISPR synthetic guide RNA (sgRNA) design generated Tbr1em2Boro (Tbr1K228E) using the CRISPOR tool. C57BL/6NJ zygotes were coinjected with Cas9 protein and single-stranded-oligodeoxynucleotide (ssODN) donor containing the patient mutation (confirmed via sequencing screening). Embryos were transplanted into pseudopregnant recipient female CD-1 mice, and founders from these litters were first mated to C57BL/6NJ breeders (JAX Stock #005304). Then, derived N1 progeny, (first identified via sequencing), were mated again to C57BL/6NJ, generating N2 mice (also identified via sequencing). N2 hets were mated for production of initial phenotyping cohorts. Tbr1K228E mice were genotyped using PCR amplification of the mutation-containing genomic region, followed by restriction enzyme digest of the PCR product.


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

Health Status Report

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Appearance

Coat Color
Black
Eye
Black

Breeding

MMRRC Breeding System
Backcross
Generation
10
Overall Breeding Performance
Good

Reproductive Statistics

Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: N/A N/A
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 7 to 9 months Greater than 12 months
Average litter size
7 to 9
Recommended wean age
4 Weeks
Average Pups Weaned
7 to 9

Order Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact OHSU Technology Transfer.

Conditions of Distribution

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 Donor is required for for-profit entities to use this strain. For more information, please contact OHSU Technology Transfer

Fees

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
075893-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $882.81
Non-Profit / For-Profit		 Aliquot Approximate quantity3
075893-UCD-RESUS Litter recovered from cryo-archive $5,892.91 / $6,181.91
Non-Profit / For-Profit		 Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu 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.