Overview

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.

Donating Investigator

Stephen P. Goff, Columbia University

Genetic overview

Genetic Background	Generation

Abl1^tm1Mlg

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Abl1	c-abl oncogene 1, non-receptor tyrosine kinase

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Developmental Biology Research
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):1153-63PubMed: 2065352 MGI: J:72875

View All References

Genetics

Abl1^tm1Mlg

Allele Symbol: Abl1^tm1Mlg

Allele Name	targeted mutation 1, Richard C Mulligan
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Richard C Mulligan; Abl1^tm1Mlg
Gene Symbol and Name	Abl1, c-abl oncogene 1, non-receptor tyrosine kinase
Gene Synonym(s)	bcr/abl; AI325092; c-ABL; E430008G22Rik; c-ABL1; v-abl; ABL; p150; E430008G22Rik; expressed sequence AI325092; JTK7; RIKEN cDNA E430008G22 gene; c-Abl; Abl; CHDSKM; BCR-ABL
Strain of Origin	129S/SvEv-Gpi1^c
Chromosome	2
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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
Developmental Biology Research
- Postnatal Lethality
  - Homozygous
- Growth Defects
  - Growth Defects (homozygous)
- Internal/Organ Defects
  - Lymphoid Tissue Defects
Reproductive Biology Research
- Fertility Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
involves: 129S/SvEv * C57BL/6J

digestive/alimentary phenotype

enlarged esophagus
- the few mutants that survive to 3-4 months of age develop megaesophagus

rectal prolapse
- the few mutants that survive to 3-4 months of age develop anal prolapse

immune system phenotype

decreased B cell number

decreased lymphocyte cell number
- 85% of mutants develop T and B cell lymphopenia

decreased T cell number

decreased thymocyte number
- thymus is severely deficient in thymocytes, with predominantly thymic stroma remaining; the few remaining thymocytes are single positives

lung inflammation
- the few mutants that survive to 3-4 months of age develop aspiration pneumonia secondary to the megaesophagus

spleen atrophy
- seen in many mutants

thymus atrophy
- seen in many mutants

liver/biliary system phenotype

abnormal hepatocyte morphology
- hepatocytes of runted pups contain fatty vacuoles and are degenerating

mammalian phenotype

cardiovascular system phenotype
- Background Sensitivity - unlike mice on a C57BL/6J congenic background, heart morphology, even in mice that die perinatally, is grossly normal

mortality/aging

decreased survivor rate
- 65% of mutants die 1-2 weeks after birth

perinatal lethality, incomplete penetrance
- about 10% are dead at birth compared to about 90% neonatal lethality on a congenic C57BL/6J background

postnatal lethality, incomplete penetrance
- 65% of mutants die 1-2 weeks after birth
- about 50% die by P14 compared to about 96% on a congenic C57BL/6J background

respiratory system phenotype

lung inflammation
- the few mutants that survive to 3-4 months of age develop aspiration pneumonia secondary to the megaesophagus

endocrine/exocrine gland phenotype

decreased thymocyte number
- thymus is severely deficient in thymocytes, with predominantly thymic stroma remaining; the few remaining thymocytes are single positives

thymus atrophy
- seen in many mutants

growth/size/body region phenotype

cachexia
- 95% of mice become runted after birth

hematopoietic system phenotype

decreased B cell number

decreased lymphocyte cell number
- 85% of mutants develop T and B cell lymphopenia

decreased T cell number

decreased thymocyte number
- thymus is severely deficient in thymocytes, with predominantly thymic stroma remaining; the few remaining thymocytes are single positives

spleen atrophy
- seen in many mutants

thymus atrophy
- seen in many mutants

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
involves: 129S/SvEv * C57BL/6J * CBA

craniofacial phenotype

decreased cranium height
- foreshortened crania are observed with high prevalence in survivors

skeleton phenotype

decreased cranium height
- foreshortened crania are observed with high prevalence in survivors

vision/eye phenotype

abnormal eye morphology
- observed in survivors

digestive/alimentary phenotype

rectal prolapse
- prolapsed recta are observed frequently in survivors

growth/size/body region phenotype

decreased body size
- observed in survivors

hematopoietic system phenotype

abnormal spleen morphology
- abnormal shape is observed with high prevalence in survivors

decreased bone marrow cell number
- variable decreases of B lymphocyte progenitors are observed

immune system phenotype

abnormal spleen morphology
- abnormal shape is observed with high prevalence in survivors

increased susceptibility to infection
- observed in survivors

mortality/aging

decreased survivor rate
- very low numbers reach weaning age; mortality among survivors continues after weaning

postnatal lethality, incomplete penetrance
- between 0 and <5% of homozygotes are detected at weaning, with significant post natal mortality being observed

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
129S/SvEv-Abl1

mortality/aging

postnatal lethality, incomplete penetrance
- about 50% die by P14 compared to about 96% on a congenic C57BL/6J background

The following phenotype relates to a compound genotype created using this strain

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
B6.129-Abl1

cardiovascular system phenotype

abnormal heart morphology
- Background Sensitivity - 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

abnormal heart ventricle morphology
- almost complete disappearance of the ventricle lumens at P0

abnormal myocardial fiber morphology
- at E18.5 mitochondria are randomly distributed and large hollow mitochondria characterized by loss of vesicles and cristae are present
- at E18.5 some sarcomeres are fragmented and disorganized with abnormal Z-discs
- nuclei shapes are highly irregular at E18.5 and P0

abnormal myocardium compact layer morphology
- the ventricular compact layer is expanded at P0

abnormal trabecula carnea morphology
- interstitial space between cardiomyocytes is increased
- Normal - no signs of fibrosis are detected
- the trabecular layer is expanded at P0

dilated heart atrium
- at E18.5

disorganized myocardium
- orientation of the fibers is highly irregular at E18.5 and P0

enlarged heart

heart hyperplasia
- at E18.5 and P0

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

increased heart ventricle size
- at E18.5

increased heart weight
- at E18.5 the heart weight to body weight ratio is increased

increased myocardial fiber number
- at E18.5 and P0

thick interventricular septum
- thicker at P0

thick ventricular wall

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

mortality/aging

neonatal lethality, incomplete penetrance
- Background Sensitivity - about 90% die between P0 an P1 compared to about 10% perinatal lethality on a mixed 129 and C57BL/6J background

postnatal lethality, incomplete penetrance
- Background Sensitivity - only 4% survive to P14 compared to about 50% survival on coisogenic 129 or mixed 129 and C57BL/6J backgrounds

muscle phenotype

abnormal myocardial fiber morphology
- at E18.5 mitochondria are randomly distributed and large hollow mitochondria characterized by loss of vesicles and cristae are present
- at E18.5 some sarcomeres are fragmented and disorganized with abnormal Z-discs
- nuclei shapes are highly irregular at E18.5 and P0

abnormal myocardium compact layer morphology
- the ventricular compact layer is expanded at P0

abnormal trabecula carnea morphology
- interstitial space between cardiomyocytes is increased
- Normal - no signs of fibrosis are detected
- the trabecular layer is expanded at P0

disorganized myocardium
- orientation of the fibers is highly irregular at E18.5 and P0

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

increased myocardial fiber number
- at E18.5 and P0

References

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):1153-63PubMed: 2065352 MGI: J:72875

Additional - Abl1^tm1Mlg related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Abl1^tm1Mlg
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, heterozygotes may be bred. Viability of homozygotes is reduced and surviving males have reduced fertility.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S-Abl1^tm1Mlg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009417 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Abl1<tm1Mlg>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

Related Products and Services

Frozen Mouse Embryo	B6.129S-Abl1<tm1Mlg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S-Abl1<tm1Mlg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S-Abl1<tm1Mlg>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S-Abl1<tm1Mlg>/J Frozen Embryo	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Abl1tm1Mlg

Allele Symbol: Abl1tm1Mlg

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Abl1tm1Mlg/Abl1tm1Mlginvolves: 129S/SvEv * C57BL/6J

digestive/alimentary phenotype

immune system phenotype

liver/biliary system phenotype

mammalian phenotype

mortality/aging

respiratory system phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Abl1tm1Mlg/Abl1tm1Mlginvolves: 129S/SvEv * C57BL/6J * CBA

craniofacial phenotype

skeleton phenotype

vision/eye phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

mortality/aging

Genotype: Abl1tm1Mlg/Abl1tm1Mlg129S/SvEv-Abl1

mortality/aging

Genotype: Abl1tm1Mlg/Abl1tm1MlgB6.129-Abl1

cardiovascular system phenotype

cellular phenotype

mortality/aging

muscle phenotype

References

Additional - Abl1tm1Mlg related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Abl1^tm1Mlg

Allele Symbol: Abl1^tm1Mlg

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
involves: 129S/SvEv * C57BL/6J

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
involves: 129S/SvEv * C57BL/6J * CBA

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
129S/SvEv-Abl1

Genotype: Abl1^tm1Mlg/Abl1^tm1Mlg
B6.129-Abl1

Additional - Abl1^tm1Mlg related