Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N8pN1 Generation Definitions   Donating Investigator Stephen P. Goff,   Columbia University

Description
These Abl1^m3 mutant mice possess a floxed neomycin resistance (neo) cassette, containing a stop codon, between exons 10 and 11 of the c-abl concogene 1, non-receptor tyrosine kinase gene, Abl1, resulting in low widespread detection of truncated protein. The allele also introduced five amino acid substitutions (Lysine to Glycine) in the first of three nuclear localization signals (NLS1) in exon 11. Mice that are heterozygous for this allele are viable, fertile, and normal in size. Homozygotes exhibit perinatal death with enlarged hearts. When these Abl1^m3 mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the neo cassette deleted in the cre-expressing tissue, resulting in restoration of gene function while retaining the NLS1 mutations, and survival past birth. When bred to mice that express a cardiac-specific α-MHC-cre transgene (see Stock No. 011038), the mice exhibit decreased proliferation of cardiac tissue and die shortly after birth. This strain may be useful for studying the growth, development, and physiology of cardiac tissue.

Development
A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette, containing a stop codon, between exons 10 and 11 of the c-abl concogene 1, non-receptor tyrosine kinase gene, Abl1. The construct also introduced five amino acid substitutions (Lysine to Glycine) in the first of three nuclear localization signals (NLS1) in exon 11. The construct was electroporated into albino B6(Cg)-Tyr^c-2J/J-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred to B6(Cg)-Tyr^c-2J/J females to establish a colony. These Abl1^m3 mice were backcrossed to B6(Cg)-Tyr^c-2J/J for at least eight 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. The Jackson Laboratory bred black mice, and they may be segregating for the Tyr^c-2J allele.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Abl1

013224	B6.129P2-Abl1tm2.1Goff/J
009417	B6.129S-Abl1tm1Mlg/J
009412	B6;129S-Abl1m1/J

View Strains carrying other alleles of Abl1     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Abl1^tm1Goff/Abl1^tm1Goff

        involves: C57BL/6

• mortality/aging
• partial perinatal lethality
  • high levels of perinatal lethality   (MGI Ref ID J:156743)
  • mice are stated to be phenotypically indistinguishable from Abl1 null mice   (MGI Ref ID J:156743)
• cardiovascular system phenotype
• abnormal heart ventricle morphology
  • decrease in the size of the ventricular lumens   (MGI Ref ID J:156743)
• • thick ventricular wall   (MGI Ref ID J:156743)
• enlarged heart   (MGI Ref ID J:156743)
• • heart hyperplasia   (MGI Ref ID J:156743)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Abl1^tm1Goff/Abl1^tm1Goff Tg(Myh6-cre)2182Mds/0

        involves: C57BL/6   (conditional)

• mortality/aging
• complete neonatal lethality
  • most die shortly after birth   (MGI Ref ID J:156743)
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • compared to homozygous mutant mice not carrying the cre transgene, cardiomyocyte overproliferation and ventricular lumen size reduction are dramatically reduced   (MGI Ref ID J:156743)
• • thick ventricular wall
    • not as thick as in homozygous mutant mice not carrying the cre transgene but slightly thicker than in heterozygous controls   (MGI Ref ID J:156743)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cardiovascular Research
Heart Abnormalities

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Abl1tm1Goff
Allele Name		targeted mutation 1, Stephen P Goff
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Abl1m3;
Mutation Made By		Stephen Goff,   Columbia University
Strain of Origin		C57BL/6
Gene Symbol and Name		Abl1, c-abl oncogene 1, non-receptor tyrosine kinase
Chromosome		2
Gene Common Name(s)		ABL; AI325092; E430008G22Rik; JTK7; RIKEN cDNA E430008G22 gene; bcr/abl; c-ABL; expressed sequence AI325092; p150; v-abl;
Molecular Note		A mutated NLS1with 5 amino acid substitutions (Lys to Gly) was introduced into exon 11 and a floxed neo cassette was introduced into intron 10 via homologous recombination. Western blot analysis revealed barely detectable levels of the full length mutant protein and low levels of a fragment consisting of the N terminal half. [MGI Ref ID J:156743]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Qiu Z; Cang Y; Goff SP. 2010. c-Abl tyrosine kinase regulates cardiac growth and development. Proc Natl Acad Sci U S A 107(3):1136-41. [PubMed: 20080568]  [MGI Ref ID J:156743]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred to wildtype littermates or C57BL/6J inbred mice (Stock No. 000664).

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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