Description

Strain Information

Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F53N1p

Appearance
gunmetal
Related Genotype: a/a Rabggta^gm/Rabggta^gm

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 Information

	Control
	Heterozygote from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Rabggta^gm allele

006937

C57BL/6J-Rabggtagm/JLlp

View Strains carrying   Rabggta^gm     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Hermansky-Pudlak Syndrome; HPS - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Rabggta^gm/Rabggta⁺

        C57BL/6J

• immune system phenotype
• defective cytotoxic T cell cytolysis (MGI Ref ID J:67600)
  • target cell lysis is slightly less than normal, but this diminution is more severe in homozygotes

Rabggta^gm/Rabggta^gm

        C57BL/6J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:13419)
  • homozygous mice have high mortality
• pigmentation phenotype
• diluted coat color (MGI Ref ID J:13419)
  • grayish black pigment dilution
  • looks like Lyst^bg
• reproductive system phenotype
• reduced fertility (MGI Ref ID J:13419)
  • homozygous mice do not breed well
• skin/coat/nails phenotype
• diluted coat color (MGI Ref ID J:13419)
  • grayish black pigment dilution
  • looks like Lyst^bg
• hematopoietic system phenotype
• abnormal megakaryocyte differentiation (MGI Ref ID J:12434)
  • megakaryocytes are more plentiful but have abnormal intracellular membranes, increased invasions by white cells and decreased platelet synthesis
• abnormal platelet morphology (MGI Ref ID J:12434)
  • platelets have abnormalities in dense granules and alpha granules with significant reductions in fibrinogen, platelet factor 4 and von Willebrand factor
• decreased platelet cell number (MGI Ref ID J:12434)
  • thrombocytopenia
• increased mean platelet volume (MGI Ref ID J:12434)
  • increased platelet size
• homeostasis/metabolism phenotype
• increased bleeding time (MGI Ref ID J:12434)
  • prolonged bleeding time
• immune system phenotype
• defective cytotoxic T cell cytolysis (MGI Ref ID J:67600)
  • reduced target cell lysis but normal secretion of granule contents hexosaminidase and granzyme A
  • in the synapse between cytotoxic T cell and target cell the granules are incompletely polarized

Rabggta^gm/Rabggta^gm

        C57BL/6J-Rabggta^gm/J

• pigmentation phenotype
• *normal* pigmentation phenotype (MGI Ref ID J:141035)
  • mice exhibit wild-type iris pigmentation

View Research Applications

Research Applications

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

Rabggta^gm related

Cell Biology Research
Vesicular Trafficking

Dermatology Research
Color and White Spotting Defects

Hematological Research
Clotting Defects
Platelet Defects (platelet storage pool deficiency)
Platelet Defects (thrombocytopenia)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Rabggtagm
Allele Name		gunmetal
Allele Type		Spontaneous
Common Name(s)		gm;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Rabggta, Rab geranylgeranyl transferase, a subunit
Chromosome		14
Gene Common Name(s)		PTAR3; gm; gunmetal;
Molecular Note		Mice carrying the gunmetal mutation have a G to A substitution in the splice site acceptor site at the 3' end of exon 1. 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. [MGI Ref ID J:52722]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

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):4144-9. [PubMed: 10737774]  [MGI Ref ID 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):1781-9. [PubMed: 7703484]  [MGI Ref ID 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):2626-35. [PubMed: 8490171]  [MGI Ref ID J:12434]

Rabggta^gm related

Anderson MG; Hawes NL; Trantow CM; Chang B; John SW. 2008. Iris phenotypes and pigment dispersion caused by genes influencing pigmentation. Pigment Cell Melanoma Res 21(5):565-78. [PubMed: 18715234]  [MGI Ref ID J:141035]

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):4144-9. [PubMed: 10737774]  [MGI Ref ID J:52722]

Dickie MM. 1964. Gunmetal Mouse News Lett 30:30.  [MGI Ref ID J:13419]

Kotti T; Head DD; McKenna CE; Russell DW. 2008. Biphasic requirement for geranylgeraniol in hippocampal long-term potentiation. Proc Natl Acad Sci U S A 105(32):11394-9. [PubMed: 18685105]  [MGI Ref ID J:140342]

McGarry MP; Reddington M; Jackson CW; Zhen L; Novak EK; Swank RT. 1999. Increased incidence and analysis of emperipolesis in megakaryocytes of the mouse mutant gunmetal. Exp Mol Pathol 66(3):191-200. [PubMed: 10486237]  [MGI Ref ID J:106334]

McGarry MP; Reddington M; Novak EK; Swank RT. 1999. Survival and lung pathology of mouse models of Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Proc Soc Exp Biol Med 220(3):162-8. [PubMed: 10193444]  [MGI Ref ID J:53228]

Nguyen T; Novak EK; Kermani M; Fluhr J; Peters LL; Swank RT; Wei ML. 2002. Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development. J Invest Dermatol 119(5):1156-64. [PubMed: 12445206]  [MGI Ref ID J:80751]

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):1781-9. [PubMed: 7703484]  [MGI Ref ID J:25033]

Stinchcombe JC; Barral DC; Mules EH; Booth S; Hume AN; Machesky LM; Seabra MC; Griffiths GM. 2001. Rab27a is required for regulated secretion in cytotoxic t lymphocytes. J Cell Biol 152(4):825-34. [PubMed: 11266472]  [MGI Ref ID J:67600]

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):2626-35. [PubMed: 8490171]  [MGI Ref ID J:12434]

Swank RT; Novak EK; McGarry MP; Zhang Y; Li W; Zhang Q; Feng L. 2000. Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome. Pigment Cell Res 13 Suppl 8:59-67. [PubMed: 11041359]  [MGI Ref ID J:103794]

Tiwari S; Italiano JE Jr; Barral DC; Mules EH; Novak EK; Swank RT; Seabra MC; Shivdasani RA. 2003. A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 102(12):3970-9. [PubMed: 12907454]  [MGI Ref ID J:86678]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Heterozygote from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

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