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 95% of all 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. During the first 3 weeks of life 7% of the homozygotes are runted and died and 6% disappear, leaving approximately 7% of homozygous mutants. 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.
