These mice carry a spontaneous mutation at the Abcg5 locus characterized by macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span.Read More +
The spontaneous mouse mutation 'thrombocytopenia and cardiomyopathy (Abcg5trac) 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 Abcg5trac 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 Abcg5trac 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.
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.
|Allele Name||thrombocytopenia and cardiomyopathy|
|Allele Synonym(s)||Abcg5trac; thrombocytopenia and cardiomyopathy|
|Gene Symbol and Name||Abcg5, ATP binding cassette subfamily G member 5|
|Gene Synonym(s)||tac; expressed sequence AW112016; cmp; Sterolin-1; trac; thrombocytopenia and cardiomyopathy; STSL; trac; AW112016|
|Strain of Origin||A/J|
|Molecular Note||Sequencing of the cDNA revealed a G-to-A mutation in exon 10 of the gene, which alters a tryptophan codon (UGG) to a premature stop codon (UAG). The premature stop codon is predicted to result the expression of a mutant protein that lacks the last 4 transmembrane domains.|
|Heterozygous or wildtype for trac|
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.
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