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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator Stephen P. Goff,   Columbia University

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.

Control Information

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

Related Strains

Strains carrying other alleles of Abl1

013225	B6(Cg)-Abl1tm1Goff/J
013224	B6.129P2-Abl1tm2.1Goff/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^tm1Mlg/Abl1^tm1Mlg

        B6.129-Abl1^tm1Mlg

• mortality/aging
• partial neonatal lethality
  • about 90% die between P0 an P1 compared to about 10% perinatal lethality on a mixed 129 and C57BL/6J background   (MGI Ref ID J:156743)
• partial postnatal lethality
  • only 4% survive to P14 compared to about 50% survival on coisogenic 129 or mixed 129 and C57BL/6J backgrounds   (MGI Ref ID J:156743)
• cardiovascular system phenotype
• abnormal heart morphology
  • defects in heart morphology develop after E14.5 and peak around birth, in contrast mice on a mixed 129 and C57BL/6J background have grossly normal heart morphology   (MGI Ref ID J:156743)
• • abnormal heart ventricle morphology
    • almost complete disappearance of the ventricle lumens at P0   (MGI Ref ID J:156743)
  • • abnormal trabecula carnea morphology
      • the trabecular layer is expanded at P0   (MGI Ref ID J:156743)
      • interstitial space between cardiomyocytes is increased   (MGI Ref ID J:156743)
      • no signs of fibrosis are detected   (MGI Ref ID J:156743)
    • increased heart ventricle size
      • at E18.5   (MGI Ref ID J:156743)
    • thick interventricular septum
      • thicker at P0   (MGI Ref ID J:156743)
    • thick ventricular wall   (MGI Ref ID J:156743)
  • abnormal myocardial fiber morphology
    • nuclei shapes are highly irregular at E18.5 and P0   (MGI Ref ID J:156743)
    • at E18.5 mitochondria are randomly distributed and large hollow mitochondria characterized by loss of vesicles and cristae are present   (MGI Ref ID J:156743)
    • at E18.5 some sarcomeres are fragmented and disorganized with abnormal Z-discs   (MGI Ref ID J:156743)
  • • increased myocardial fiber number
      • at E18.5 and P0   (MGI Ref ID J:156743)
  • abnormal myocardium compact layer morphology
    • the ventricular compact layer is expanded at P0   (MGI Ref ID J:156743)
  • dilated heart atrium
    • at E18.5   (MGI Ref ID J:156743)
  • disorganized myocardium
    • orientation of the fibers is highly irregular at E18.5 and P0   (MGI Ref ID J:156743)
  • enlarged heart   (MGI Ref ID J:156743)
  • • heart hyperplasia
      • at E18.5 and P0   (MGI Ref ID J:156743)
    • increased heart weight
      • at E18.5 the heart weight to body weight ratio is increased   (MGI Ref ID J:156743)
• increased fetal cardiomyocyte proliferation
  • at E18.5 the numbers of mitotic cells are modestly increased in the ventricles and interventricular septum and the increase in mitosis is primarily confined to cardiomyocytes   (MGI Ref ID J:156743)
• muscle phenotype
• abnormal myocardial fiber morphology
  • nuclei shapes are highly irregular at E18.5 and P0   (MGI Ref ID J:156743)
  • at E18.5 mitochondria are randomly distributed and large hollow mitochondria characterized by loss of vesicles and cristae are present   (MGI Ref ID J:156743)
  • at E18.5 some sarcomeres are fragmented and disorganized with abnormal Z-discs   (MGI Ref ID J:156743)
• • increased myocardial fiber number
    • at E18.5 and P0   (MGI Ref ID J:156743)
• abnormal trabecula carnea morphology
  • the trabecular layer is expanded at P0   (MGI Ref ID J:156743)
  • interstitial space between cardiomyocytes is increased   (MGI Ref ID J:156743)
  • no signs of fibrosis are detected   (MGI Ref ID J:156743)
• increased fetal cardiomyocyte proliferation
  • at E18.5 the numbers of mitotic cells are modestly increased in the ventricles and interventricular septum and the increase in mitosis is primarily confined to cardiomyocytes   (MGI Ref ID J:156743)
• cellular phenotype
• increased fetal cardiomyocyte proliferation
  • at E18.5 the numbers of mitotic cells are modestly increased in the ventricles and interventricular septum and the increase in mitosis is primarily confined to cardiomyocytes   (MGI Ref ID J:156743)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Abl1^tm1Mlg/Abl1^tm1Mlg

        involves: 129S/SvEv * C57BL/6J

• mortality/aging
• decreased survivor rate
  • 65% of mutants die 1-2 weeks after birth   (MGI Ref ID J:72875)
• partial perinatal lethality
  • about 10% are dead at birth compared to about 90% neonatal lethality on a congenic C57BL/6J background   (MGI Ref ID J:156743)
• partial postnatal lethality
  • 65% of mutants die 1-2 weeks after birth   (MGI Ref ID J:72875)
  • about 50% die by P14 compared to about 96% on a congenic C57BL/6J background   (MGI Ref ID J:156743)
• growth/size phenotype
• cachexia
  • 95% of mice become runted after birth   (MGI Ref ID J:72875)
• immune system phenotype
• decreased lymphocyte cell number
  • 85% of mutants develop T and B cell lymphopenia   (MGI Ref ID J:72875)
• • decreased B cell number   (MGI Ref ID J:72875)
  • decreased T cell number   (MGI Ref ID J:72875)
  • • decreased thymocyte number
      • thymus is severely deficient in thymocytes, with predominantly thymic stroma remaining; the few remaining thymocytes are single positives   (MGI Ref ID J:72875)
• lung inflammation
  • the few mutants that survive to 3-4 months of age develop aspiration pneumonia secondary to the megaesophagus   (MGI Ref ID J:72875)
• spleen atrophy
  • seen in many mutants   (MGI Ref ID J:72875)
• thymus atrophy
  • seen in many mutants   (MGI Ref ID J:72875)
• digestive/alimentary phenotype
• abnormal esophagus morphology
  • the few mutants that survive to 3-4 months of age develop megaesophagus   (MGI Ref ID J:72875)
• rectal prolapse
  • the few mutants that survive to 3-4 months of age develop anal prolapse   (MGI Ref ID J:72875)
• liver/biliary system phenotype
• abnormal hepatocyte morphology
  • hepatocytes of runted pups contain fatty vacuoles and are degenerating   (MGI Ref ID J:72875)
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • unlike mice on a C57BL/6J congenic background, heart morphology, even in mice that die perinatally, is grossly normal   (MGI Ref ID J:156743)
• hematopoietic system phenotype
• decreased lymphocyte cell number
  • 85% of mutants develop T and B cell lymphopenia   (MGI Ref ID J:72875)
• • decreased B cell number   (MGI Ref ID J:72875)
  • decreased T cell number   (MGI Ref ID J:72875)
  • • decreased thymocyte number
      • thymus is severely deficient in thymocytes, with predominantly thymic stroma remaining; the few remaining thymocytes are single positives   (MGI Ref ID J:72875)
• spleen atrophy
  • seen in many mutants   (MGI Ref ID J:72875)
• thymus atrophy
  • seen in many mutants   (MGI Ref ID J:72875)
• respiratory system phenotype
• lung inflammation
  • the few mutants that survive to 3-4 months of age develop aspiration pneumonia secondary to the megaesophagus   (MGI Ref ID J:72875)

Abl1^tm1Mlg/Abl1^tm1Mlg

        involves: 129S/SvEv * CBA * C57BL/6J

• mortality/aging
• decreased survivor rate
  • very low numbers reach weaning age; mortality among survivors continues after weaning   (MGI Ref ID J:34643)
• partial postnatal lethality
  • between 0 and <5% of homozygotes are detected at weaning, with significant post natal mortality being observed   (MGI Ref ID J:34643)
• growth/size phenotype
• decreased body size
  • observed in survivors   (MGI Ref ID J:34643)
• craniofacial phenotype
• decreased cranium height
  • foreshortened crania are observed with high prevalence in survivors   (MGI Ref ID J:34643)
• digestive/alimentary phenotype
• rectal prolapse
  • prolapsed recta are observed frequently in survivors   (MGI Ref ID J:34643)
• hematopoietic system phenotype
• abnormal spleen morphology
  • abnormal shape is observed with high prevalence in survivors   (MGI Ref ID J:34643)
• decreased bone marrow cell number
  • variable decreases of B lymphocyte progenitors are observed   (MGI Ref ID J:34643)
• immune system phenotype
• abnormal spleen morphology
  • abnormal shape is observed with high prevalence in survivors   (MGI Ref ID J:34643)
• increased susceptibility to infection
  • observed in survivors   (MGI Ref ID J:34643)
• skeleton phenotype
• decreased cranium height
  • foreshortened crania are observed with high prevalence in survivors   (MGI Ref ID J:34643)
• vision/eye phenotype
• abnormal eye morphology
  • observed in survivors   (MGI Ref ID J:34643)

Abl1^tm1Mlg/Abl1^tm1Mlg

        129S/SvEv-Abl1^tm1Mlg

• mortality/aging
• partial postnatal lethality
  • about 50% die by P14 compared to about 96% on a congenic C57BL/6J background   (MGI Ref ID J:156743)

View Research Applications

Research Applications

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

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)
Internal/Organ Defects
      Lymphoid Tissue Defects
Postnatal Lethality
      Homozygous

Immunology, Inflammation and Autoimmunity Research
Lymphoid Tissue Defects

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Abl1tm1Mlg
Allele Name		targeted mutation 1, Richard C Mulligan
Allele Type		Targeted (knock-out)
Common Name(s)		Abl2; abl-; ablm2; c-Abl-; c-abl2;
Mutation Made By		Dr. Richard Mulligan,   Harvard Medical School
Strain of Origin		129S/SvEv-Gpi1
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 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. [MGI Ref ID J:72875]

Genotyping

Genotyping Information

Genotyping Protocols

Abl1^tm1Mlg, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tybulewicz VL; Crawford CE; Jackson PK; Bronson RT; Mulligan RC. 1991. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 65(7):1153-63. [PubMed: 2065352]  [MGI Ref ID J:72875]

Additional References

Abl1^tm1Mlg related

Borges HL; Hunton IC; Wang JY. 2007. Reduction of apoptosis in Rb-deficient embryos via Abl knockout. Oncogene 26(26):3868-77. [PubMed: 17173068]  [MGI Ref ID J:122882]

Chen S; Wang R; Li QF; Tang DD. 2009. Abl knockout differentially affects p130 Crk-associated substrate, vinculin, and paxillin in blood vessels of mice. Am J Physiol Heart Circ Physiol 297(2):H533-9. [PubMed: 19542491]  [MGI Ref ID J:151088]

Gourley SL; Koleske AJ; Taylor JR. 2009. Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine. Proc Natl Acad Sci U S A 106(39):16859-64. [PubMed: 19805386]  [MGI Ref ID J:153211]

Gourley SL; Olevska A; Warren MS; Taylor JR; Koleske AJ. 2012. Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. J Neurosci 32(7):2314-23. [PubMed: 22396406]  [MGI Ref ID J:181612]

Hardin JD; Boast S; Mendelsohn M; de los Santos K; Goff SP. 1996. Transgenes encoding both type I and type IV c-abl proteins rescue the lethality of c-abl mutant mice. Oncogene 12(12):2669-77. [PubMed: 8700526]  [MGI Ref ID J:34643]

Kain KH; Klemke RL. 2001. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J Biol Chem 276(19):16185-92. [PubMed: 11279004]  [MGI Ref ID J:116356]

Kharbanda S; Pandey P; Jin S; Inoue S; Bharti A; Yuan ZM; Weichselbaum R; Weaver D; Kufe D. 1997. Functional interaction between DNA-PK and c-Abl in response to DNA damage. Nature 386(6626):732-5. [PubMed: 9109492]  [MGI Ref ID J:116399]

Kharbanda S; Pandey P; Morris PL; Whang Y; Xu Y; Sawant S; Zhu LJ; Kumar N; Yuan ZM; Weichselbaum R; Sawyers CL; Pandita TK; Kufe D. 1998. Functional role for the c-Abl tyrosine kinase in meiosis I. Oncogene 16(14):1773-7. [PubMed: 9583675]  [MGI Ref ID J:124453]

Koleske AJ; Gifford AM; Scott ML; Nee M; Bronson RT; Miczek KA; Baltimore D. 1998. Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron 21(6):1259-72. [PubMed: 9883720]  [MGI Ref ID J:51887]

Kua HY; Liu H; Leong WF; Li L; Jia D; Ma G; Hu Y; Wang X; Chau JF; Chen YG; Mishina Y; Boast S; Yeh J; Xia L; Chen GQ; He L; Goff SP; Li B. 2012. c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16INK4a expression. Nat Cell Biol 14(7):727-37. [PubMed: 22729085]  [MGI Ref ID J:190763]

Lam QL; Lo CK; Zheng BJ; Ko KH; Osmond DG; Wu GE; Rottapel R; Lu L. 2007. Impaired V(D)J recombination and increased apoptosis among B cell precursors in the bone marrow of c-Abl-deficient mice. Int Immunol 19(3):267-76. [PubMed: 17229817]  [MGI Ref ID J:118698]

Lee Y; Barnes DE; Lindahl T; McKinnon PJ. 2000. Defective neurogenesis resulting from DNA ligase IV deficiency requires Atm Genes Dev 14(20):2576-80. [PubMed: 11040211]  [MGI Ref ID J:65540]

Li B; Boast S; de los Santos K; Schieren I; Quiroz M; Teitelbaum SL; Tondravi MM; Goff SP. 2000. Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation. Nat Genet 24(3):304-8. [PubMed: 10700189]  [MGI Ref ID J:60749]

Li B; Wang X; Rasheed N; Hu Y; Boast S; Ishii T; Nakayama K; Nakayama KI; Goff SP. 2004. Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C delta. Genes Dev 18(15):1824-37. [PubMed: 15289456]  [MGI Ref ID J:119329]

Liberatore RA; Goff SP. 2009. c-Abl-deficient mice exhibit reduced numbers of peritoneal B-1 cells and defects in BCR-induced B cell activation. Int Immunol 21(4):403-14. [PubMed: 19228876]  [MGI Ref ID J:147102]

Liberatore RA; Goff SP; Nunes I. 2009. NF-kappaB activity is constitutively elevated in c-Abl null fibroblasts. Proc Natl Acad Sci U S A 106(42):17823-8. [PubMed: 19805123]  [MGI Ref ID J:153689]

Miller HL; Lee Y; Zhao J; Chong MJ; McKinnon PJ. 2003. Atm and c-Abl cooperate in the response to genotoxic stress during nervous system development. Brain Res Dev Brain Res 145(1):31-8. [PubMed: 14519491]  [MGI Ref ID J:86191]

Moresco EM; Scheetz AJ; Bornmann WG; Koleske AJ; Fitzsimonds RM. 2003. Abl family nonreceptor tyrosine kinases modulate short-term synaptic plasticity. J Neurophysiol 89(3):1678-87. [PubMed: 12626632]  [MGI Ref ID J:103041]

Nunes I; Higgins RD; Zanetta L; Shamamian P; Goff SP. 2001. c-abl is required for the development of hyperoxia-induced retinopathy. J Exp Med 193(12):1383-91. [PubMed: 11413193]  [MGI Ref ID J:70012]

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]

Wang X; Kua HY; Hu Y; Guo K; Zeng Q; Wu Q; Ng HH; Karsenty G; de Crombrugghe B; Yeh J; Li B. 2006. p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling. J Cell Biol 172(1):115-25. [PubMed: 16380437]  [MGI Ref ID J:104404]

Wang X; Zeng L; Wang J; Chau JF; Lai KP; Jia D; Poonepalli A; Hande MP; Liu H; He G; He L; Li B. 2011. A positive role for c-Abl in Atm and Atr activation in DNA damage response. Cell Death Differ 18(1):5-15. [PubMed: 20798688]  [MGI Ref ID J:186979]

Wetzel DM; McMahon-Pratt D; Koleske AJ. 2012. The abl and arg kinases mediate distinct modes of phagocytosis and are required for maximal leishmania infection. Mol Cell Biol 32(15):3176-86. [PubMed: 22665498]  [MGI Ref ID J:186633]

Whang YE; Tran C; Henderson C; Syljuasen RG; Rozengurt N; McBride WH; Sawyers CL. 2000. c-Abl is required for development and optimal cell proliferation in the context of p53 deficiency. Proc Natl Acad Sci U S A 97(10):5486-91. [PubMed: 10805805]  [MGI Ref ID J:62221]

Yaqoob U; Cao S; Shergill U; Jagavelu K; Geng Z; Yin M; de Assuncao TM; Cao Y; Szabolcs A; Thorgeirsson S; Schwartz M; Yang JD; Ehman R; Roberts L; Mukhopadhyay D; Shah VH. 2012. Neuropilin-1 stimulates tumor growth by increasing fibronectin fibril assembly in the tumor microenvironment. Cancer Res 72(16):4047-59. [PubMed: 22738912]  [MGI Ref ID J:191030]

Zipfel PA; Grove M; Blackburn K; Fujimoto M; Tedder TF; Pendergast AM. 2000. The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19 J Immunol 165(12):6872-9. [PubMed: 11120811]  [MGI Ref ID J:66085]

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 maintained as a live colony, heterozygotes may be bred. Viability of homozygotes is reduced and surviving males have reduced fertility.

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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See Terms of Use tab for General Terms and Conditions

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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