This targeted mutation of the T cell receptor beta chain gene is severely deficient in thymocytes and CD4+ CD8+ cells and may be useful in studies involving T cell receptors.
Mice homozygous for the Tcrbtm1Mom targeted mutation are viable and fertile. Mice are deficient in alpha beta T-cell receptor. The total number of cells in the thymus is ~8% that of wild-type; CD4+CD8+ cells ~6% of wild-type. 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. Mice may develop inflammatory bowel disease beginning at ~4-6 months of age.
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.
This targeted mutant strain 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. This strain was generated in the laboratory of Dr. Leonard Shultz by backcrossing mice from B6.129P2-Tcrbtm1Mom/J (002118) to BALB/cByJ inbred mice for a minimum of 10 generations.
|Allele Name||targeted mutation 1, Peter Mombaerts|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CBeta-; TCR-Cbeta-; TCRb-; TCRbeta-; beta-|
|Gene Symbol and Name||Tcrb, T cell receptor beta chain|
|Gene Synonym(s)||TCRbeta; Tib; Tib|
|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.