Mice homozygous for the Rabggtagm allele are grayish-black on a non-agouti background due to pigment dilution. Eye color is not affected. Homozygotes have reduced viability and do not breed well. These mutants have a prolonged bleeding time. Although gunmetal mice have an increased number of megakariocytes, they have about half the number platelets found in wildtype siblings. This decrease in platelet number results from a slower rate of platelet synthesis. These platelets are heterogeneous in size and are larger than normal, but have fewer dense granules per platelet and approximately half of the normal level of serotonin. The prolonged bleeding time and decreased platelet count and volume can be transferred to wildtype mice through bone marrow transplantion. Likewise bone marrow transplants from wildtype mice reversed the platelet deficiency in gunmetal recipients. Western blots of platelet extracts showed a decrease in fibrinogen, von Willebrand factor, and platel...
Read More +Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Rabggta | Rab geranylgeranyl transferase, a subunit |
Mice homozygous for the Rabggtagm allele are grayish-black on a non-agouti background due to pigment dilution. Eye color is not affected. Homozygotes have reduced viability and do not breed well. These mutants have a prolonged bleeding time. Although gunmetal mice have an increased number of megakariocytes, they have about half the number platelets found in wildtype siblings. This decrease in platelet number results from a slower rate of platelet synthesis. These platelets are heterogeneous in size and are larger than normal, but have fewer dense granules per platelet and approximately half of the normal level of serotonin. The prolonged bleeding time and decreased platelet count and volume can be transferred to wildtype mice through bone marrow transplantion. Likewise bone marrow transplants from wildtype mice reversed the platelet deficiency in gunmetal recipients. Western blots of platelet extracts showed a decrease in fibrinogen, von Willebrand factor, and platelet factor 4, but von Willebrand factor in serum plasma is increased in these mutants. Electron microscopy of megakaryocytes from these mutants revealed that the demarcation membranes are not homogeneously distributed and an increased percentage of megakaryocytes are undergoing emperipolesis. This emperipolesis can produce false increases in apparent ploidy in flow cytometry of these megakariocytes. Gunmetal platelets also have unusual membrane complexes including elongated, striated inclusion granules and profiles of Golgi complex. In keeping with the expression pattern of Rab27, no abnormalities were detected in white or red blood cells. (Dickie, 1964; Swank et al., 1993; Novak et al., 1995; McGarry et al., 1999.)
The gunmetal mutation arose spontaneously in a C57BL/6J colony at The Jackson Laboratory in 1962 and was maintained by sibling intercrossing. Embryos were cryopreserved in 1980 using C57BL/6J females bred with homozygous males at generation F53.
Allele Name | gunmetal |
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Allele Type | Spontaneous |
Allele Synonym(s) | gm |
Gene Symbol and Name | Rabggta, Rab geranylgeranyl transferase, a subunit |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 14 |
Molecular Note | Mice carrying the gunmetal mutation have a G-to-A substitution in the splice site acceptor site at the 3' end of intron 1. It eliminates the exon 2 splice acceptor by changing it from CAG to CAA, leading to mis-splicing. RT-PCR of extracts from gunmetal mice yielded two transcripts, a dominant 429 base pair transcript that lacks exon 1 and is predicted not to encode functional protein, and the 638 base pair, intron alpha retaining transcript found in wildtype mice. RABGGTA protein and enzymatic activity are found in gunmetal mice, but both are reduced by 70% relative to wildtype siblings. |
When using the C57BL/6J-Rabggtagm/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000110 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Rabggta<gm> |
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