Strain Name:
C57BL/6-Lig4tiny/Mmucd
Stock Number:
031685-UCD
Citation ID:
RRID:MMRRC_031685-UCD
Other Names:
Tiny, STOCK Apb-Lig4tiny/Apb/Mmcd

Strain Information

Lig4tiny
Name: ligase IV, DNA, ATP-dependent; tiny
Synonyms: Lig4Y288C, ENU4AT:013
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Chemically Induced
Lig4
Name: ligase IV, DNA, ATP-dependent
Synonyms: DNA ligase IV, 5830471N16Rik, tiny
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Chemically Induced
NCBI: 319583
HGNC: HGNC:6601
Homologene: 1736
Genetic Alterations
The tiny mutation is an ENU-induced A to G transition at position 1161 in the catalytic domain in exon 2. This mutation results in a Tyrosine to Cysteine amino acid change at position 288.
Genotype Determination
Phenotype
Homozygous: Animal model for human LIGIV Syndrome. Small stature. Severe combined immune deficiency. Hypogammaglobulinemia, no antibody response to immunization, very few circulating B or T cells. Hemopoiesis defect. Hypoplastic anemia, hemopoietic stem cells unable to transplant, poorly proliferative in tissue culture, unable to compete with transplanted wild-type hemopoietic stem cells even in the absence of any conditioning regime. Non-homologous end-joining DNA repair defect. Reduced DNA ligase IV protein levels and enzymatic activity. Western blot and immunofluorescent analysis of extracts from homozygous mutant mouse embryonic fibroblasts (MEFs) reveal 5-fold reduction in the protein level. Although the mutant protein complexes stably with XRCC4, in vivo adenylation activity is reduced 10-fold in mutant versus wild type MEFs.

Mammalian Phenotype Terms
Allelic Composition: Lig4tiny/Lig4tiny (Genetic Background: C57BL/6-Lig4tiny )

MeSH Terms
  • Animals
  • Antibody Formation/immunology
  • Cell Differentiation/immunology
  • Cell Survival
  • DNA Ligases/deficiency
  • DNA Ligases/genetics
  • DNA Ligases/metabolism
  • Disease Models, Animal
  • Immunoglobulin Class Switching/immunology
  • Immunoglobulin Isotypes/immunology
  • Lymphocytes/cytology
  • Lymphocytes/enzymology
  • Lymphocytes/immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation/genetics
  • Syndrome
  • Thymus Neoplasms/enzymology
  • Thymus Neoplasms/genetics
  • Thymus Neoplasms/immunology
  • Thymus Neoplasms/pathology
  • Aging/physiology
  • Cell Proliferation
  • Cellular Senescence/physiology
  • DNA Breaks, Double-Stranded
  • DNA Damage
  • DNA Ligase ATP
  • DNA Repair
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/pathology
  • Humans
  • Mutation, Missense/drug effects
  • Mutation, Missense/genetics
Strain Development
ENU-induced mutation in male C57BL/6 mouse. Heterozygotes were crossed to a (C57BL/6 x B10.BR-H2k) F1 hybrid and the colony was maintained by sibling matings.
Suggested Control Mice
  • Wild-type littermates or 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 mmrrc@ucdavis.edu. Older strains may not have this information.
  • Developmental biology
  • Hematology
  • Immunology and inflammation
  • Models for human disease
    • - human LigIV Syndrome
Donor
Chris Goodnow, BVSc, PhD, The Australian National University, Canberra, Australia
Primary Reference
  • Nijnik A, Dawson S, Crockford TL, Woodbine L, Visetnoi S, Bennett S, Jones M, Turner GD, Jeggo PA, Goodnow CC, Cornall RJ. Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome. J Clin Invest. 2009 Jun;119(6):1696-705. doi: 10.1172/JCI32743. Epub 2009 May 18. (Medline PMID:19451691)
  • Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C, Rodrigues NP, Crockford TL, Cabuy E, Vindigni A, Enver T, Bell JI, Slijepcevic P, Goodnow CC, Jeggo PA, Cornall RJ. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 2007 Jun 7;447(7145):686-90. (Medline PMID:17554302)

Colony and Husbandry Information

This strain is also reposited as Tiny at the NHMRC Australian PhenomeBank (APB).

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 .
Coat Color
Black
MMRRC Breeding System
Other or uncertain
Breeding Scheme(s)
  • Homozygotes are severe combined immunodeficient. Donor suggests breeding het x het.
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: Unknown Unknown
Average litter size
6
Recommended wean age
3 weeks

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@ucdavis.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
031685-UCD-RESUS Litter recovered from cryo-archive $5,055.00 / Non-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.

Some MMRRC strains were submitted by the donor as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality of this material. We have extensive experience with recovery of mice from cryopreserved sperm and embryos of varying quality, including using techniques such as IVF and ICSI, and are confident that we will have success in most, if not all, cases. However, because of the unknown quality of these frozen samples, we will restrict recovery efforts to two attempts for each order. Subsequent attempts can be performed on a fee-for-service basis, in addition to the standard fees, upon request.

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.