B6.129S-Abl1^tm1Mlg/J

Stock number: 009417
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research

Description

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.

Detailed description

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.

Development

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 backcrossed to C57BL/6 for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Abl1^tm1Mlg
Name: targeted mutation 1, Richard C Mulligan
MGI accession ID: MGI:2153718
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Abl1
Marker name: c-abl oncogene 1, non-receptor tyrosine kinase
Chromosome: 2
Strain of origin: 129S/SvEv-Gpi1^c
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.