In this strain, the targeted mutation replaces exon 5 and part of exon 6 of the c-abl concogene 1, non-receptor tyrosine kinase gene, Abl1 with a neomycin resistance (neo) cassette, abolishing gene function. These mice may be useful for studying cell proliferation, survival and migration, as well as lymphopoesis and hematopoiesis.
Stephen P. Goff, Columbia University
In this strain, the targeted mutation replaces exon 5 and part of exon 6 of the c-abl concogene 1, non-receptor tyrosine kinase gene, Abl1, with a neomycin resistance (neo) cassette, abolishing gene function. Mice heterozygous for this allele are viable, fertile, and normal in size. Homozygous c-Abl2 mice exhibit no abnormal phenotype before birth. After birth 10% of homozygotes die, while 95% of the remaining homozygotes become runted and 85% develop lymphopenia. During the first week of age fatty vacuoles are evident in hepatocytes and some hepatic degeneration is evident. Spleens are severely atrophied, as are thymuses which show a severe deficiency in thymocytes. The few remaining thymocytes are only single positive CD4 or CD8 T cells. Only 50% of homozygous mutants survive the first 2 weeks of life . The few that survived to 3 or 4 months of age exhibited megaesophagus, anal prolapsed, aspiration pneumonia, and signs of infection in the nasal passages and ears. Mutants weighing 50% of the weight of controls had 50% fewer bone marrow cells, whereas mutant thymocytes decreased 20- to 500-fold in number. These mice may be useful for studying cell proliferation, survival and migration, as well as lymphopoesis and hematopoiesis.
A targeting vector was designed to replace exon 5 and part of exon 6 of the c-abl concogene 1, non-receptor tyrosine kinase gene, Abl1 with a neomycin resistance (neo) cassette. The construct was electroporated into 129S/SvEv-Gpic-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred to C57BL/6 females to establish a colony. These c-Abl2 mice were then backcrossed to 129S/SvEv mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Richard C Mulligan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||abl-; Abl2; ablm2; c-Abl-; c-abl2|
|Gene Symbol and Name||Abl1, c-abl oncogene 1, non-receptor tyrosine kinase|
|Strain of Origin||129S/SvEv-Gpi1c|
|Molecular Note||A genomic fragment containing exon 5 and part of exon 6 was replaced by a neomycin resistance cassette. These sequences encode the N-terminal part of the tyrosine kinase domain, including the nucleotide and ATP binding sites.|
|Mutations Made By|| |
Dr. Richard Mulligan, Harvard Medical School
When maintained as a live colony, heterozygotes may be bred. Viability of homozygotes is reduced and surviving males have reduced fertility.
When using the 129S(B6)-Abl1tm1Mlg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009416 in your Materials and Methods section.