Mice homozygous for the Tcrbtm1Mom targeted mutation are deficient in alpha beta T-cell receptor and may be useful when studying diabetes.
Maki Nakayama, U of Colorado School of Medicine
Mice homozygous for the Tcrbtm1Mom targeted mutation are viable and fertile. Mice are deficient in T cells expressing alpha beta T-cell receptor. The total number of cells in the thymus is ~8% that of wildtype; CD4+CD8+ cells ~6% of wildtype. The proportion of CD4-CD8- (IL2 receptor positive) cells increases to about 50% of the total cell number. Alpha beta thymocyte differentiation is blocked at an earlier stage than the Tcratm1Mom strain. There is normal differentiation of gamma delta thymocytes. Homozygous mice do not develop diabetes and pancreatic islets are free of lymphacytic infiltration at 30 weeks of age. Heterozygous mice develop diabetes and insulitis.
The Tcrbtm1Mom mutant was developed by Dr. Peter Mombaerts in the laboratory of Dr. Susumu Tonegawa at the Center for Cancer Research, Massachusetts Institute of Technology. A targeting replacement vector was used which resulted in a 15-kb deletion encompassing the Tcrb locus from J-beta-1.3 to downstream of C-beta-2. The mutant contains the Pgk-neo gene in reverse transcriptional orientation. The 129-derived E14 ES cell line was used. The C57BL/6J strain (Stock No. 002118) was generated by backcrossing mice carrying the Tcrbtm1Mom mutation to C57BL/6J inbred mice (Stock No. 000664) for 12 generations. These mice were bred to mice carrying the Tg(DO11.10)10Dlo transgene, and subsequently to NOD/ShiLtJ mice (Stock No. 001976) for 12 generations to produce this Stock No. 023082. The Tg(DO11.10)10Dlo transgene was bred out of this strain.
|Allele Name||targeted mutation 1, Peter Mombaerts|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||beta-; CBeta-; TCRb-; TCRbeta-; TCR-Cbeta-|
|Gene Symbol and Name||Tcrb, T cell receptor beta chain|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||15kb of sequence was replaced with a PGK-neo cassette. The deletion included one of the two D gene segments, ten of the twelve J gene segments, and both constant gene segments.|
|Mutations Made By|| |
Peter Mombaerts, Max Planck Research Unit for Neurogenetics
This Tcrbtm1Mom strain is maintained by mating homozygous siblings. This strain should be housed under conditions similar to Prkdcscid/Prkdcscid mice or any other immunodeficient strain.
When using the TCRbeta- mouse strain in a publication, please cite the originating article(s) and include JAX stock #023082 in your Materials and Methods section.