In these mice, a β-galactosidase sequence, a neomycin (neo) resistance gene, and a polyadenylation signal interrupt exon 2 of the RAS guanyl releasing protein 1 (Rasgrp1) gene, abolishing gene expression. RasGRP1 is a guanine nucleotide-releasing factor needed for activation of the Ras-Erk1/2 pathway. RasGRP1 plays an important role in development, homeostasis and differentiation of thymocytes. Homozygous mice are viable and fertile. The exhibit a deficiency of mature, single-positive αβ (CD4+CD8- and CD4-CD8+) thymocytes in thymus, with normal numbers of immature thymocytes. They contain increased numbers of CD4-CD8+ γδ T cells in the peripheral lymphoid organs, which do not produce IL-17 upon activation. γδ T cell numbers in the thymus were normal. They have increased numbers of CD138+ plasma cells.
A targeting vector was designed to insert a β-galactosidase sequence, a neomycin (neo) resistance gene, and a polyadenylation signal into exon 2 of the RAS guanyl releasing protein 1 (Rasgrp1) gene. The construct was electroporated into 129P3/J-derived embryonic stem (ES) cells and correctly targeted clones were injected into C57BL/6J blastocysts. Male chimeric mice were mated with C57BL/6J females to produce heterozygotes, offspring were mated to produce homozygotes. They were bred to C57BL/6J mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, James C Stone|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Rasgrp1, RAS guanyl releasing protein 1|
|Strain of Origin||129P3/J|
|General Note||ES cell line = NX1.|
|Molecular Note||Exon 2 was disrupted by the insertion of a cassette containing both Beta-galactosidase and neomycin resistance genes. While the translation of a fusion protein containing residues 1 through 16 of the endogenous joined to the Beta-galactosidase protein was expected, such a polypeptide was undetected by Western blot analysis of thymus and spleen extracts obtained from homozygous mutant mice.|
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129P3-Rasgrp1tm1Jstn/TbwnJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #022353 in your Materials and Methods section.