NOD.129S2(B6)-Tlx1^tm1Sjk/DvsJ

Stock number: 019142
Research areas: Developmental Biology Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research

Description

This strain provides an asplenic NOD that develops diabetes with the same incidence as standard NOD mice.

Detailed description

Mice homozygous for the Tlx1^tm1Sjk 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). Tlx1^tm1Sjk 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 Tlx1^tm1Sjk allele was backcrossed from the strain B6.129S2-Tlx1^tm1Sjk/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.

Allele

Symbol: Tlx1^tm1Sjk
Name: targeted mutation 1, Stanley J Korsmeyer
MGI accession ID: MGI:1857260
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tlx1
Marker name: T cell leukemia, homeobox 1
Chromosome: 19
Strain of origin: 129S2/SvPas
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.