Strain Name:

NOD.129S2(B6)-Tlx1tm1Sjk/DvsJ

Stock Number:

019142

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
This strain provides an asplenic NOD that develops diabetes with the same incidence as standard NOD mice.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain NOD/ShiLtJ
Donor Strain 129S2 via D3 ES cell line
H2 Haplotypeg7
GenerationN10F5pN1
Generation Definitions
 
Donating InvestigatorDr. David Serreze,   The Jackson Laboratory

Appearance
albino
Related Genotype: A/A Tyrc/Tyrc

Description
Mice homozygous for the Tlx1tm1Sjk targeted mutation on this NOD congenic background do not differ in diabetes incidence from standard NOD controls and thymic T and B cell profiles are normal even though these homozygotes are asplenic. The outward appearance looks like that of the NOD host background, with no obvious limb abnormalities (D.V. Serreze, personal communication). Tlx1tm1Sjk homozygotes have been finely characterized on other genetic backgrounds and found to lack a spleen; however, all other internal organs were found to be normal. Characteristics reported included: polydactyly or oligodactyly of the hindlimbs, tibial hemimelia, and sometimes reduction of the femur and pubic element of the pelvic girdle. Pharyngeal and mastication muscles derived from the branchial arches were reported to be present and anatomically normal homozygotes had normal cranial ganglia morphology and position and normal cranial motor nuclei function. Also reported were normal numbers of RBCs but increased numbers of WBCs, including neutrophils and lymphocytes. The B-cell and T-cell profile was described as normal in the thymus, lymph nodes and peripheral blood. Many erythrocytes had nuclear fragments (Howell-Jolly bodies).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
This congenic strain was generated by Dr. David Serreze at The Jackson Laboratory. The Tlx1tm1Sjk allele was backcrossed from the strain B6.129S2-Tlx1tm1Sjk/J (stock #002771) onto the NOD/ShiLtDvs background for 10 generations before sibling inbreeding to homozygosity. Sperm was cryopreserved from homozygous males at generation N10F5 and NOD/ShiLtJ females are used for recovery by in vitro fertilization.

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tlx1tm1Sjk allele
002771   B6.129S2-Tlx1tm1Sjk/J
002273   B6;129S2-Tlx1tm1Sjk/J
View Strains carrying   Tlx1tm1Sjk     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Tlx1tm1Sjk/Tlx1tm1Sjk

        involves: 129S2/SvPas
  • hematopoietic system phenotype
  • abnormal spleen development
    • at E12.5, mutant embryos display no cellular organization or mesenchymal cell condensation at the site of splenic development   (MGI Ref ID J:17695)
    • at E13.5, mutant embryos show no histological evidence of a splenic primordium within the dorsal mesogastrium   (MGI Ref ID J:17695)
    • abnormal spleen mesenchyme morphology
      • at E12.5, mutant embryos display no mesenchymal cell condensation at the site of splenic development, indicating a specific, localized defect in mesodermal cells destined to form the spleen   (MGI Ref ID J:17695)
  • absent spleen
    • all adult homozygotes appear externally normal but display complete absence of spleen   (MGI Ref ID J:17695)
    • in contrast, all other internal organs (including the stomach and pancreas) are normal in morphology and position   (MGI Ref ID J:17695)
  • increased leukocyte cell number
    • homozygotes display a ~2-fold increase in the number of white blood cells relative to wild-type mice   (MGI Ref ID J:17695)
    • however, the B-cell and T-cell profile is normal in thymus, lymph node and peripheral blood   (MGI Ref ID J:17695)
    • increased lymphocyte cell number
      • in peripheral blood smears   (MGI Ref ID J:17695)
    • increased neutrophil cell number
      • in peripheral blood smears   (MGI Ref ID J:17695)
  • increased number of Howell-Jolly bodies
    • many erythrocytes contain nuclear fragments of condensed DNA known as Howell-Jolly bodies, commonly associated with asplenia   (MGI Ref ID J:17695)
    • however, complete blood counts indicate that the number of red blood cells is normal   (MGI Ref ID J:17695)
  • immune system phenotype
  • abnormal spleen development
    • at E12.5, mutant embryos display no cellular organization or mesenchymal cell condensation at the site of splenic development   (MGI Ref ID J:17695)
    • at E13.5, mutant embryos show no histological evidence of a splenic primordium within the dorsal mesogastrium   (MGI Ref ID J:17695)
    • abnormal spleen mesenchyme morphology
      • at E12.5, mutant embryos display no mesenchymal cell condensation at the site of splenic development, indicating a specific, localized defect in mesodermal cells destined to form the spleen   (MGI Ref ID J:17695)
  • absent spleen
    • all adult homozygotes appear externally normal but display complete absence of spleen   (MGI Ref ID J:17695)
    • in contrast, all other internal organs (including the stomach and pancreas) are normal in morphology and position   (MGI Ref ID J:17695)
  • increased leukocyte cell number
    • homozygotes display a ~2-fold increase in the number of white blood cells relative to wild-type mice   (MGI Ref ID J:17695)
    • however, the B-cell and T-cell profile is normal in thymus, lymph node and peripheral blood   (MGI Ref ID J:17695)
    • increased lymphocyte cell number
      • in peripheral blood smears   (MGI Ref ID J:17695)
    • increased neutrophil cell number
      • in peripheral blood smears   (MGI Ref ID J:17695)
  • embryogenesis phenotype
  • *normal* embryogenesis phenotype
    • despite observed gene expression in the branchial region of wild-type mice, homozygotes display no detectable abnormalities in branchial arches   (MGI Ref ID J:17695)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • despite observed gene expression in the developing hindbrain and cranial ganglia of wild-type mice, homozygotes display no detectable abnormalities in the hindbrain, cranial ganglia or cranial motor nuclei   (MGI Ref ID J:17695)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
Type 1 Diabetes (IDDM) Analysis Strains

Tlx1tm1Sjk related

Developmental Biology Research
Internal/Organ Defects
      asplenic

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Internal/Organ Research
Spleen Defects
      asplenic

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tlx1tm1Sjk
Allele Name targeted mutation 1, Stanley J Korsmeyer
Allele Type Targeted (knock-out)
Common Name(s) Hox11-; Tlx-; Tlx1-;
Mutation Made ByDr. Stanley Korsmeyer,   Dana-Farber Cancer Institute
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Tlx1, T cell leukemia, homeobox 1
Chromosome 19
Gene Common Name(s) HOX11; Hox-11; RGD1563655; TCL3; homeo box-11 cluster;
Molecular Note Exon 1 was disrupted by the insertion of a neomycin selection cassette into codon 53. Transcript was undetected by in situ hybridization of homozygous mutant mice. [MGI Ref ID J:17695]

Genotyping

Genotyping Information

Genotyping Protocols

Tlx1tm1Sjkalternate1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Roberts CW; Shutter JR; Korsmeyer SJ. 1994. Hox11 controls the genesis of the spleen. Nature 368(6473):747-9. [PubMed: 7908720]  [MGI Ref ID J:17695]

Additional References

Tlx1tm1Sjk related

Brendolan A; Ferretti E; Salsi V; Moses K; Quaggin S; Blasi F; Cleary ML; Selleri L. 2005. A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny. Development 132(13):3113-26. [PubMed: 15944191]  [MGI Ref ID J:99062]

Cheng L; Arata A; Mizuguchi R; Qian Y; Karunaratne A; Gray PA; Arata S; Shirasawa S; Bouchard M; Luo P; Chen CL; Busslinger M; Goulding M; Onimaru H; Ma Q. 2004. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat Neurosci 7(5):510-7. [PubMed: 15064766]  [MGI Ref ID J:90585]

Guo Z; Zhao C; Huang M; Huang T; Fan M; Xie Z; Chen Y; Zhao X; Xia G; Geng J; Cheng L. 2012. Tlx1/3 and ptf1a control the expression of distinct sets of transmitter and Peptide receptor genes in the developing dorsal spinal cord. J Neurosci 32(25):8509-20. [PubMed: 22723691]  [MGI Ref ID J:185665]

Herzer U; Crocoll A; Barton D; Howells N; Englert C. 1999. The Wilms tumor suppressor gene wt1 is required for development of the spleen. Curr Biol 9(15):837-40. [PubMed: 10469569]  [MGI Ref ID J:56651]

Hu J; Huang T; Li T; Guo Z; Cheng L. 2012. c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections. J Neurosci 32(16):5362-73. [PubMed: 22514301]  [MGI Ref ID J:184447]

Huang M; Huang T; Xiang Y; Xie Z; Chen Y; Yan R; Xu J; Cheng L. 2008. Ptf1a, Lbx1 and Pax2 coordinate glycinergic and peptidergic transmitter phenotypes in dorsal spinal inhibitory neurons. Dev Biol 322(2):394-405. [PubMed: 18634777]  [MGI Ref ID J:142008]

Karrer U; Althage A; Odermatt B; Roberts CW; Korsmeyer SJ; Miyawaki S ; Hengartner H ; Zinkernagel RM. 1997. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. J Exp Med 185(12):2157-70. [PubMed: 9182687]  [MGI Ref ID J:41084]

Lakkis FG; Arakelov A; Konieczny BT; Inoue Y. 2000. Immunologic 'ignorance' of vascularized organ transplants in the absence of secondary lymphoid tissue. Nat Med 6(6):686-8. [PubMed: 10835686]  [MGI Ref ID J:118716]

Moens CB; Selleri L. 2006. Hox cofactors in vertebrate development. Dev Biol 291(2):193-206. [PubMed: 16515781]  [MGI Ref ID J:109563]

Qian Y; Shirasawa S; Chen CL; Cheng L; Ma Q. 2002. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1. Genes Dev 16(10):1220-33. [PubMed: 12023301]  [MGI Ref ID J:76655]

Roberts CW; Sonder AM; Lumsden A; Korsmeyer SJ. 1995. Development expression of Hox11 and specification of splenic cell fate. Am J Pathol 146(5):1089-101. [PubMed: 7747804]  [MGI Ref ID J:25198]

Wardemann H; Boehm T; Dear N; Carsetti R. 2002. B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen. J Exp Med 195(6):771-80. [PubMed: 11901202]  [MGI Ref ID J:75706]

Xu Y; Lopes C; Qian Y; Liu Y; Cheng L; Goulding M; Turner EE; Lima D; Ma Q. 2008. Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons. J Neurosci 28(15):4037-46. [PubMed: 18400903]  [MGI Ref ID J:134327]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3175.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4127.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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