Strain Name:
B6(Cg)-Otoftm2.1(cre/ERT2)Mull/Mmmh
Stock Number:
032782-MU
Citation ID:
RRID:MMRRC_032782-MU
Major Collection:

Strain Information

Otoftm2.1(cre/ERT2)Mull
Name: otoferlin; targeted mutation 2.1, Ulrich Mueller
Synonyms: Otof-CreERT2
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 5
Alteration at locus: Targeted Mutation
cre
Name: cre recombinase
Type: Gene
Species: Enterobacteria phage P1 (bacteriophage P1)
Chromosome:
Alteration at locus: Targeted Mutation
Otof
Name: otoferlin
Type: Gene
Species: Mouse
Chromosome: 5
Alteration at locus: Targeted Mutation
NCBI: 83762
HGNC: HGNC:8515
Homologene: 12892
Genotype Determination
ES Cell Line
Not specified
Phenotype
The Otof-CreERT2 "knock-in" allele has the CreERT2 fusion protein (CreERT2 fusion protein) inserted into the first coding ATG of the otoferlin (Otof) locus; this was designed to both abolish Otof gene function (see details below) and place CreERT2 expression under the control of the Otof promoter/enhancer elements. The donating investigator reports that homozygous mice are viable and fertile. Although other mice with homozygous deletion of Otof exhibit deafness and abnormal cochlear inner hair cell physiology/morphology, the donating investigator has not yet determined the Otof-CreERT2 homozygous phenotype (see details below). Cre-ERT2 fusion gene activity is inducible; observed following taxomifen administration. As such, when Otof-CreERT2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Otof-expressing cells of the offspring. The donating investigator reports they did not test tamoxifen-inducible Cre recombinase activity.

The overall phenotype, Otof expression, and Cre-ERT2 expression of these Otof-CreERT2 mice is expected to be the same as Otof-Cre mice harboring a NLS-Cre "knocked-in" to the same region of the Otof locus (see MMRRC:032781-MU). . The Otof-Cre phenotype is summarized below:
Although other mice with homozygous deletion of Otof gene function exhibit deafness and abnormal cochlear inner hair cell physiology/morphology, the donating investigator reports that Otof-Cre homozygous mice are not deaf via auditory brainstem response assays (the presence of any subtle inner ear or vestibular defects has not yet been characterized). The donating investigator has not determined if the Otof-Cre allele abolishes expression of a functional Otof mRNA/protein, or if it retains expression of some functional splice variant of Otof. The donating investigator reports Cre recombinase activity is observed in cochlear and vestibular hair cells, as well as a very small patch of cells in the ventral forebrain. When tested in the entire embryo at embryonic day (E)12.5, the donating investigator reports that Cre recombinase activity was only observed in these same tissues.

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17beta-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

Mammalian Phenotype Terms
Allelic Composition: Otoftm2.1(cre/ERT2)Mull/Otof+ (Genetic Background: involves: C57BL/6 * NZB * SJL )

  • phenotype not analyzed
Strain Development
A targeting vector was designed to insert a CreERT2 fusion gene (Cre-ERT2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), an SV40 polyA signal, and an FRT-flanked PGK-Neo cassette into the initiation codon of the otoferlin (Otof) locus. This construct was electroporated into C57BL/6-derived Bruce4 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6 mice to establish the colony. Next, mutant mice were bred with FLPe-expressing mice on a C57BL/6 congenic background to remove the FRT-flanked PGK-Neo cassette. The resulting Otof-CreERT2 mice were then bred to C57BL/6J inbred mice for approximately two generations (selecting away from the FLPe transgene) prior to arrival at The Jackson Laboratory.
Suggested Control Mice
  • Wildtype littermates
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 mmrrc@missouri.edu. Older strains may not have this information.
Donor
Ulrich Mueller, Ph.D., The Scripps Research Institute

Colony and Husbandry Information

When maintained as a live colony, homozygous mice may be bred together.

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@missouri.edu.

Order Request Information

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@missouri.edu 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
032782-MU-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
032782-MU-RESUS Litter recovered from cryo-archive $2,624.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.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.