Overview

Also Known As:thrombocytopenia and cardiomyopathy

These mice carry a spontaneous mutation at the Abcg5 locus characterized by macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span.

Genetic overview

Genetic Background	Generation

Abcg5^trac

Allele Type	Gene Symbol	Gene Name
Spontaneous	Abcg5	ATP binding cassette subfamily G member 5

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Research Applications

Cardiovascular Research
Hematological Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The spontaneous mouse mutation 'thrombocytopenia and cardiomyopathy (Abcg5^trac) causes macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold decrease in platelet numbers and a 3-fold increase in platelet size with structural alterations and functional impairments in activation and aggregation. Megakaryocytes in homozygous mice are present in increased numbers, have poorly developed demarcation membrane systems, and have decreased polyploidy. The thrombocytopenia is not intrinsic to defects at the level of hematopoietic progenitor cells but is associated with a microenvironmental abnormality. The Abcg5^trac mutation maps to mouse chromosome 17, syntenic with human chromosome 2p21-22. A G to A mutation in exon 10 of the adenosine triphosphate (ATP)-binding cassette subfamily G, member 5 gene, alters a tryptophan codon (UGG) to a premature stop codon (UAG). Crosses with mice doubly transgenic for the human ABCG5 and ABCG8 genes rescued platelet counts and volumes. ABCG5 and ABCG8 form a functional complex that limits dietary phytosterol accumulation. Phytosterolemia in homozygous mice confirmed a functional defect in the ABCG5/ABCG8 transport system. The Abcg5^trac mutation provides a new clinically significant animal model for human phytosterolemia and provides a new means for studying the role of phytosterols in hematologic diseases and testing therapeutic interventions.

Development

The thrombocytopenia and cardiomyopathy (trac) mutation arose spontaneously on the A/J inbred strain at The Jackson Laboratory in 1989 and was initially called cardiomyopathy, cmp. It was maintained by closed colony inbreeding, primarily sibling inbreeding, and in 1991 embryos were cryopreserved from +/? females bred with heterozygous males all between generation F7 and F11.

Genetics

Abcg5^trac

Allele Symbol: Abcg5^trac

Allele Name	thrombocytopenia and cardiomyopathy
Allele Type	Spontaneous
Allele Synonym(s)	cardiomyopathy; cmp; tac
Gene Symbol and Name	Abcg5, ATP binding cassette subfamily G member 5
Gene Synonym(s)
Strain of Origin	A/J
Chromosome	17
Molecular Note	Sequencing of the cDNA revealed a G-to-A mutation in exon 10 of the gene, which alters a tryptophan codon 462 (UGG) to a premature stop codon (UAG) (p.W462*). The premature stop codon is predicted to result the expression of a mutant protein that lacks the last 4 transmembrane domains.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Abcg5^trac related

Cardiovascular Research
- Heart Abnormalities
  - cardiomyopathy
Hematological Research
- Platelet Defects
  - thrombocytopenia

Mammalian Phenotype Terms by Genotype

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

Genotype: Abcg5^trac/Abcg5^trac
A/J-Abcg5

behavior/neurological phenotype

hunched posture
- at 12 weeks of age

cardiovascular system phenotype

cardiac fibrosis
- multifocal myocardial fibrosis

cardiomyopathy

homeostasis/metabolism phenotype

abnormal circulating cholesterol level
- esterified cholesterol levels are decreased to one-half those found in plasma from littermates, although free cholesterol levels do not differ

abnormal circulating lipid level
- plasma levels of plant sterols including free and esterified sitosterol, stigmasterol, brassicasterol, and campesterol are significantly elevated

abnormal platelet activation
- a decrease in the platelet activation response by 11 weeks of age

decreased platelet aggregation
- at 11 weeks of age, have impaired platelet aggregation

increased bleeding time
- greatly increased bleeding times following amputation of the tail tip

immune system phenotype

abnormal neutrophil morphology
- increase in the percentage of neutrophils

decreased leukocyte cell number
- 2-fold reduction in the numbers of white blood cells

mortality/aging

premature death
- mean lifespan is shortened
- progressive decline and death by 4 to 6 months of age

cellular phenotype

abnormal megakaryocyte differentiation
- bone marrow and spleen megakaryocytes most commonly underwent only one endomitosis to a ploidy of 4N

muscle phenotype

cardiomyopathy

reproductive system phenotype

abnormal spermatogenesis
- sperm are present in testicular tubules but only a few degenerate sperm are seen in the epididymis (spermatic abiotrophy)

female infertility
- females are infertile
- however, when ovaries are transferred to ovarectomized immunodeficient recipients matings to wild-type mice produce heterozygous mutant pups

male infertility

growth/size/body region phenotype

decreased body size
- at 12 weeks of age

hematopoietic system phenotype

abnormal erythrocyte osmotic lysis
- increase in red blood cell fragility

abnormal megakaryocyte differentiation
- bone marrow and spleen megakaryocytes most commonly underwent only one endomitosis to a ploidy of 4N

abnormal megakaryocyte morphology
- absence of a well defined demarcation membrane system with membranes taking on a spherical or bubble like appearance
- the endoplasmic reticulum is more prominent and dilated, there is a reduction in the number of alpha granules and dense bodies, and a wider peripheral zone

abnormal megakaryocyte progenitor cell morphology
- 2-fold increase in the number of megakaryocyte progenitors in the bone marrow at 19 to 34 weeks of age

abnormal neutrophil morphology
- increase in the percentage of neutrophils

abnormal platelet activation
- a decrease in the platelet activation response by 11 weeks of age

abnormal platelet alpha-granule morphology
- increased number of small, immature alpha-granules per platelet

abnormal platelet morphology
- beta-1 tubulin-stained platelets have a more intense staining and an increase in the diameter of the microtubule coils
- by TEM, an increase in the number of small, immature alpha-granules and in the numbers of mitochondria
- TEM shows the scattered remnants of rough endoplasmic reticulum normally lost during platelet maturation and absence of normal microtubular elements

anisocytosis
- in peripheral blood smears, at 6 to 10 weeks of age

decreased hematocrit
- in young adults

decreased leukocyte cell number
- 2-fold reduction in the numbers of white blood cells

decreased platelet aggregation
- at 11 weeks of age, have impaired platelet aggregation

giant platelets
- at 6 to 10 weeks of age, greatly enlarged platelets are present in peripheral blood smears

hemolytic anemia
- mild regenerative hemolytic anemia

increased erythrocyte osmotic fragility
- increase in red blood cell fragility

increased mean platelet volume
- at 10 to 17 weeks of age, show a 3-fold increase in platelet volume

increased megakaryocyte cell number
- at 6 to 10 weeks of age, occasional megakaryocytes are seen in the peripheral blood
- FACS analysis of 4-8 week-old mouse bone marrow shows a 4-fold increase in percentages of CD41+CD61+ megakaryocytes
- histologically in bone marrow, spleen and lung

reticulocytosis
- twice the number of reticulocytes

stomatocytosis
- stomatocytes are present in peripheral blood smears, at 6 to 10 weeks of age

thrombocytopenia
- at 10 to 17 weeks of age, show a 20-fold reduction in platelet numbers
- however, at weaning platelet numbers are normal

References

Additional - Abcg5^trac related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Abcg5
- Genotyping resources and troubleshooting
Citation
When using the thrombocytopenia and cardiomyopathy mouse strain in a publication, please cite the originating article(s) and include JAX stock #001830 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/Product	Description	Price
	Heterozygous or wildtype for trac

Payment Terms and Conditions

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:thrombocytopenia and cardiomyopathy

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Abcg5trac

Allele Symbol: Abcg5trac

Disease Terms

Research Areas By Phenotype

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

Genotype: Abcg5trac related

Mammalian Phenotype Terms by Genotype

Genotype: Abcg5trac/Abcg5tracA/J-Abcg5

behavior/neurological phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

cellular phenotype

muscle phenotype

reproductive system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

References

Additional - Abcg5trac related

Genotyping Protocols

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Abcg5^trac

Allele Symbol: Abcg5^trac

Genotype: Abcg5^trac related

Genotype: Abcg5^trac/Abcg5^trac
A/J-Abcg5

Additional - Abcg5^trac related