Overview

Mice homozygous for the Rabggta^gm 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...

Genetic overview

Genetic Background	Generation

Rabggta^gm

Allele Type	Gene Symbol	Gene Name
Spontaneous	Rabggta	Rab geranylgeranyl transferase, a subunit

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Research Applications

Dermatology Research
Hematological Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Rabggta^gm 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.)

Development

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.

Control Suggestions

Heterozygote from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Rabggta^gm

Allele Symbol: Rabggta^gm

Allele Name	gunmetal
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.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Hermansky-Pudlak syndrome

Research Areas By Phenotype

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

Genotype: Rabggta^gm related

Dermatology Research
- Color and White Spotting Defects
Hematological Research
- Clotting Defects
- Platelet Defects
  - platelet storage pool deficiency
  - thrombocytopenia
Cell Biology Research
- Vesicular Trafficking

Mammalian Phenotype Terms by Genotype

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

Genotype: Rabggta^gm/Rabggta^gm
C57BL/6J-Rabggta

cellular phenotype

abnormal megakaryocyte differentiation
- megakaryocytes are more plentiful but have abnormal intracellular membranes, increased invasions by white cells and decreased platelet synthesis

homeostasis/metabolism phenotype

decreased platelet serotonin level
- serotonin concentration is reduced to less than 50% of control values

increased bleeding time
- prolonged bleeding time

immune system phenotype

decreased cytotoxic T cell cytolysis
- in the synapse between cytotoxic T cell and target cell the granules are incompletely polarized
- reduced target cell lysis but normal secretion of granule contents hexosaminidase and granzyme A

integument phenotype

diluted coat color
- grayish black pigment dilution
- looks like Lyst^bg

mortality/aging

premature death
- homozygous mice have high mortality

nervous system phenotype

decreased platelet serotonin level
- serotonin concentration is reduced to less than 50% of control values

hematopoietic system phenotype

abnormal megakaryocyte differentiation
- megakaryocytes are more plentiful but have abnormal intracellular membranes, increased invasions by white cells and decreased platelet synthesis

abnormal platelet alpha-granule morphology
- plasma vWF levels are increased concomitant with the platelet vWF reduction
- platelet alpha granules show significant reductions in fibrinogen, platelet factor 4, and von Willebrand factor (vWF)

decreased cytotoxic T cell cytolysis
- in the synapse between cytotoxic T cell and target cell the granules are incompletely polarized
- reduced target cell lysis but normal secretion of granule contents hexosaminidase and granzyme A

decreased platelet dense granule number
- number of dense granules per platelet is reduced to ~50% of control values, as detected by whole mount electron microscopy

decreased platelet serotonin level
- serotonin concentration is reduced to less than 50% of control values

increased mean platelet volume
- 30% increase in mean platelet volume
- platelet size difference is maintained from 4 weeks to 6 months of age

thrombocytopenia
- platelet counts are ~50% of those in heterozygous controls

pigmentation phenotype

diluted coat color
- grayish black pigment dilution
- looks like Lyst^bg

reproductive system phenotype

reduced fertility
- homozygous mice do not breed well

Genotype: Rabggta^gm/Rabggta⁺
C57BL/6J-Rabggta

hematopoietic system phenotype

decreased cytotoxic T cell cytolysis
- target cell lysis is slightly less than normal, but this diminution is more severe in homozygotes

immune system phenotype

decreased cytotoxic T cell cytolysis
- target cell lysis is slightly less than normal, but this diminution is more severe in homozygotes

Genotype: Rabggta^gm/Rabggta^gm
C57BL/6J-Rabggta/J

mammalian phenotype

pigmentation phenotype
- Normal - mice exhibit wild-type iris pigmentation

References

Additional References

Detter JC; Zhang Q; Mules EH; Novak EK; Mishra VS; Li W; McMurtrie EB; Tchernev VT; Wallace MR; Seabra MC; Swank RT; Kingsmore SF. 2000. Rab geranylgeranyl transferase alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet synthesis. Proc Natl Acad Sci U S A 97(8):4144-9PubMed: 10737774 MGI: J:52722
Novak EK; Reddington M; Zhen L; Stenberg PE; Jackson CW; McGarry MP; Swank RT. 1995. Inherited thrombocytopenia caused by reduced platelet production in mice with the gunmetal pigment gene mutation. Blood 85(7):1781-9PubMed: 7703484 MGI: J:25033
Swank RT; Jiang SY; Reddington M; Conway J; Stephenson D; McGarry MP; Novak EK. 1993. Inherited abnormalities in platelet organelles and platelet formation and associated altered expression of low molecular weight guanosine triphosphate-binding proteins in the mouse pigment mutant gunmetal. Blood 81(10):2626-35PubMed: 8490171 MGI: J:12434

Additional - Rabggta^gm related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- gunmetal
  Related Genotype: a/a Rabggta^gm/Rabggta^gm
Citation
When using the C57BL/6J-Rabggta^gm/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000110 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Rabggta<gm>

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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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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Rabggtagm

Allele Symbol: Rabggtagm

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Rabggtagm related

Mammalian Phenotype Terms by Genotype

Genotype: Rabggtagm/RabggtagmC57BL/6J-Rabggta

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

mortality/aging

nervous system phenotype

hematopoietic system phenotype

pigmentation phenotype

reproductive system phenotype

Genotype: Rabggtagm/Rabggta+C57BL/6J-Rabggta

hematopoietic system phenotype

immune system phenotype

Genotype: Rabggtagm/RabggtagmC57BL/6J-Rabggta/J

mammalian phenotype

References

Additional References

Additional - Rabggtagm related

Genotyping Protocols

Appearance

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

Rabggta^gm

Allele Symbol: Rabggta^gm

Genotype: Rabggta^gm related

Genotype: Rabggta^gm/Rabggta^gm
C57BL/6J-Rabggta

Genotype: Rabggta^gm/Rabggta⁺
C57BL/6J-Rabggta

Genotype: Rabggta^gm/Rabggta^gm
C57BL/6J-Rabggta/J

Additional - Rabggta^gm related