Strain Name:
B6.Cg-Tia1tm1Andp Smn1tm5(Smn1/SMN2)Mrph/Mmjax
Stock Number:
065937-JAX
Citation ID:
RRID:MMRRC_065937-JAX
Other Names:
Smnc/c/Tia1-/-

Gene Information

Smn1tm5(Smn1/SMN2)Mrph
Name: survival motor neuron 1; targeted mutation 5, Andrew Murphy
Synonyms: Smn allele C
Type: Allele
Species: Multi-species
Chromosome: 13
Alteration at locus: Knock-In
Smn1
Name: survival motor neuron 1
Synonyms: SMN
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 13
Alteration at locus: Knock-In
NCBI: 20595
Homologene: 292
SMN2
Name: survival of motor neuron 2, centromeric
Type: Gene
Species: Homo sapiens (human)
Chromosome: 5
Alteration at locus: Knock-In
Tia1tm1Andp
Name: cytotoxic granule-associated RNA binding protein 1; targeted mutation 1, Paul Anderson
Synonyms: TIA-1-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Targeted Mutation
Tia1
Name: cytotoxic granule-associated RNA binding protein 1
Synonyms: mTIA-1, 2310050N03Rik
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 6
Alteration at locus: Targeted Mutation
NCBI: 21841
Homologene: 20692
Genetic Alterations
The Tia1 gene was disrupted by replacement of parts of intron 3 and exon 4 of the genomic DNA with a neomycin cassette via homologous recombination.

The Smn1tm5(Smn1/SMN2)Mrph allele encodes two coding sequences: the first is a hybrid gene in which a 2.2-kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 gene was replaced with a 1.3-kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 gene and the second is a full, 42-kb copy of the human SMN2 gene. A selection cassette located downstream from the human SMN2 polyadenylation signal was removed by FLPe expression in ES cells leaving an FRT site at the downstream junction between human and mouse DNA. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes.
ES Cell Line
  • Tia1 allele: D3 derived from 129S2/SvPas
  • Smn1 allele: F1H4 derived from (129S6/SvEvTac x C57BL/6NTac)F1
Phenotype
The allele C (C+/+, official: Smn1tm5(Smn1/SMN2)Mrph) mouse recapitulates a mild spinal muscular atrophy (SMA)-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN1 exon 7 splicing. In humans, TIA1 is reported to be downregulated in obese patients. The donor showed that female Tia1-knockout (Tia1−/−) mice gain significant body weight during early postnatal development. Underscoring the opposing effects of Tia1 deletion and low SMN1 level on body weight gain, both C+/+ and C+/+/Tia1−/− females showed a similar body weight gain trajectory. Early tail necrosis was observed in C+/+/Tia1−/− females but not in males. There was impairment of male reproductive organ development and exacerbation of the C+/+/Tia1−/− testis transcriptome. These findings implicate a protein factor as a gender-specific modifier in this mouse model of SMA.
MeSH Terms
  • Alleles
  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Genes, Modifier
  • Genotype
  • Male
  • Mice
  • Mice, Knockout
  • Muscular Atrophy, Spinal/diagnosis
  • Muscular Atrophy, Spinal/genetics
  • Muscular Atrophy, Spinal/physiopathology
  • Necrosis/genetics
  • Necrosis/pathology
  • Organogenesis/genetics
  • Phenotype
  • Severity of Illness Index
  • Sex Factors
  • T-Cell Intracellular Antigen-1/genetics
  • Testis/embryology
  • Testis/metabolism
  • Testis/pathology
  • Transcriptome
  • 3' Untranslated Regions
  • Cytokines/biosynthesis
  • Gene Expression Regulation
  • Macrophages, Peritoneal/immunology
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Mice, Mutant Strains
  • Protein Biosynthesis
  • Proteins
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism
  • Shock, Septic/mortality
  • T-Cell Intracellular Antigen-1
  • Tumor Necrosis Factor-alpha/genetics
  • Behavior, Animal
  • Humans
  • Mice, Inbred Strains
  • Neuromuscular Junction/genetics
  • Neuromuscular Junction/metabolism
  • Survival of Motor Neuron 1 Protein/genetics
  • Survival of Motor Neuron 1 Protein/metabolism
  • Survival of Motor Neuron 2 Protein/genetics
  • Survival of Motor Neuron 2 Protein/metabolism
Strain Development
This is strain is a cross of two strains, B6.129-Smn1tm5(Smn1/SMN2)Mrph/J (JAX Strain #008714) and a strain carrying the Tia1tm1Andp allele on the C57BL/6 background (PMID:10921895).
Suggested Control Mice
Wild-type C57BL/6J (control for both, Smnc/c and Tia1 knockout) and/or B6.129-Smn1tm5(Smn1/SMN2)Mrph/J (RRID:IMSR_JAX:00714) as control for Tia1 knockout.
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Immunology and Inflammation
  • Internal/Organ
  • Models for Human Disease
  • Neurobiology
  • Reproduction
  • Research Tools
Donor
Ravindra N. Singh, Ph.D., Iowa State University.
Paul Anderson, M.D., Harvard Medical School, Brigham and Women's Hospital.
Andrew Murphy, Ph.D., Regeneron Pharmaceuticals.
Primary Reference

Howell MD, Ottesen EW, Singh NN, Anderson RL, Seo J, Sivanesan S, Whitley EM, Singh RN. TIA1 is a gender-specific disease modifier of a mild mouse model ofspinal muscular atrophy. Sci Rep. 2017 Aug 3;7(1):7183. doi:10.1038/s41598-017-07468-2. (Medline PMID: 28775379)

Piecyk M, Wax S, Beck AR, Kedersha N, Gupta M, Maritim B, Chen S, Gueydan C,Kruys V, Streuli M, Anderson P. TIA-1 is a translational silencer thatselectively regulates the expression of TNF-alpha. EMBO J. 2000 Aug1;19(15):4154-63. (Medline PMID: 10921895)

Osborne M, Gomez D, Feng Z, McEwen C, Beltran J, Cirillo K, El-Khodor B, LinMY, Li Y, Knowlton WM, McKemy DD, Bogdanik L, Butts-Dehm K, Martens K, Davis C,Doty R, Wardwell K, Ghavami A, Kobayashi D, Ko CP, Ramboz S, Lutz C.Characterization of behavioral and neuromuscular junction phenotypes in a novelallelic series of SMA mouse models. Hum Mol Genet. 2012 Oct 15;21(20):4431-47.Epub 2012 Jul 16. (Medline PMID: 22802075)

Colony and Husbandry Information

In the donor's laboratory, the mice werehoused under the standard conditions with a 12-h light/dark cycle, constant temperature (22±1ºC), and humidity (relative, 30%). All mice had free access to food and water.
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 csmmrrc@jax.org .
Coat Color
Black
Eye
Black
MMRRC Breeding System
Backcross and random intra-strain mating
Generation
N2 (C57BL/6), F14+
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Reduced
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Variable Variable
Average litter size
Variable
Recommended wean age
3 Weeks
Average Pups Weaned
Variable

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 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
065937-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
065937-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
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.