Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Pascal Goldschmidt-Clermont,   University of Miami Miller School of Med

Description
Mice that are homozygous for the transgene are viable, fertile and normal in size. Males develop reddish, discolored tail lesions beginning at 8 months of age. Females develop tumors at approximately 18 months. Tumors exhibit many characteristics of Kaposi's sarcoma including an increase in spindle cells without identifiable vascular structures, slits containing red blood cells and hemosiderin between cells, expression of phenotypic markers (such as CD31, CD34, and von Willebrand factor), and an association with male gender. Transgenic mice exhibit moderate hypertension, left ventricular hypertrophy, accelerated wound healing and increased vascular formation in response to wound grafting. This mutant mouse strain may be useful in studies of blood pressure, angiogenesis, wound healing, oxidative stress and Kaposi's sarcoma.

Development
A transgenic construct containing the constitutively active glycine to valine mutation at amino acid 12 (G12V) of the human RAC1 gene under the control of mouse smooth muscle alpha actin (Acta2) promoter. This transgene was microinjected into single-cell stage FVB/N pronuclei. Founder line 33 was subsequently established. The mice were then crossed to FVB/N by the donating laboratory.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Acta2

005129

C.Cg-Tg(Acta2/CYSLTR1)31Fun/J

View Strains carrying other alleles of Acta2     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Kaposi Sarcoma

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tg(Acta2-RAC1*G12V)33Pjgc/0

        involves: C57BL/6 * FVB/N

• tumorigenesis
• sarcoma
  • mice develop Kaposi-like tumors at a lower prevalence than in homozygotes   (MGI Ref ID J:150015)

Tg(Acta2-RAC1*G12V)33Pjgc/Tg(Acta2-RAC1*G12V)33Pjgc

        involves: C57BL/6 * FVB/N

• tumorigenesis
• sarcoma
  • at 8 months mice develop discolored reddish lesions mainly on the tail unlike wild-type mice   (MGI Ref ID J:150015)
  • mice develop Kaposi-like tumors with excessive proliferation of spindle cells without identifiable organized vascular structures inside the tumors but with slits containing red blood cells and hemosiderin between cells unlike in wild-type mice   (MGI Ref ID J:150015)
  • tumors prevalence is more severe in older, males homozygotes   (MGI Ref ID J:150015)
  • female mice develop Kaposi-like sarcomas later in life (mean age 18 months)   (MGI Ref ID J:150015)
  • tumors cells are positive for Kaposi sarcoma phenotypic markers CD31 and CD34   (MGI Ref ID J:150015)
  • tumor cells secrete more IL6, IL8, TNF-alpha, MCP1, MIP1alpha, and KC than in smooth muscle cells   (MGI Ref ID J:150015)
  • tumors exhibit increased reactive oxygen species-mediated oxidative DNA damage compared to in wild-type cells   (MGI Ref ID J:150015)
  • tumors cells exhibit polyploidy and aneuploidy   (MGI Ref ID J:150015)
  • tumors exhibit a two-fold increase in reactive oxygen species production compared with wild-type cells   (MGI Ref ID J:150015)
  • tumor cell growth is inhibited by N-acetyl-cysteine and stimulated by hydrogen peroxide   (MGI Ref ID J:150015)
  • however, treatment with N-acetyl-cysteine prevents limits the development of tumors   (MGI Ref ID J:150015)
• immune system phenotype
• abnormal chemokine secretion
  • tumor cells secrete more MCP1, MIP1alpha, and KC than in smooth muscle cells   (MGI Ref ID J:150015)
• increased interleukin-6 secretion
  • in tumor cells compared with smooth muscle cells   (MGI Ref ID J:150015)
• increased tumor necrosis factor secretion
  • in tumor cells compared with smooth muscle cells   (MGI Ref ID J:150015)
• cellular phenotype
• aneuploidy
  • in tumor cells   (MGI Ref ID J:150015)
• oxidative stress
  • tumors exhibit a two-fold increase in reactive oxygen species production compared with wild-type cells   (MGI Ref ID J:150015)
• polyploidy
  • in tumor cells   (MGI Ref ID J:150015)

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence
      Other Tissues/Organs
      Other Tissues/Organs: multiple

Cardiovascular Research
Heart Abnormalities
Hypertension
Vascular Defects

Internal/Organ Research
Wound Healing
      enhanced

Research Tools
Cancer Research
      tumor immunology

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tg(Acta2-RAC1*G12V)33Pjgc
Allele Name		transgene insertion 33, Pascal J Goldschmidt-Clermont
Allele Type		Transgenic (random, expressed)
Common Name(s)		RacCA;
Strain of Origin		FVB/N
Expressed Gene		RAC1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), human
Promoter		Acta2, actin, alpha 2, smooth muscle, aorta, mouse, laboratory
Molecular Note		The cDNA coding for human RAC1 was mutated with a glycine 12 to valine substitution. The cDNA of RacCA, including its polyadenylation tail, was cloned within the Smp-8 plasmid that contained a 3.6 kb segment of the 5 kb-region of SMA promoter. The SMA promoter was used to induce selective overexpression of RacCA in SMCs. The purified fragment was microinjectedinto fertilized mouse eggs from FVB/N females, [MGI Ref ID J:150479]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hassanain HH; Gregg D; Marcelo ML; Zweier JL; Souza HP; Selvakumar B; Ma Q; Moustafa-Bayoumi M; Binkley PF; Flavahan NA; Morris M; Dong C; Goldschmidt-Clermont PJ. 2007. Hypertension caused by transgenic overexpression of Rac1. Antioxid Redox Signal 9(1):91-100. [PubMed: 17115888]  [MGI Ref ID J:150479]

Additional References

Tg(Acta2-RAC1*G12V)33Pjgc related

Hassanain HH; Irshaid F; Wisel S; Sheridan J; Michler RE; Goldschmidt-Clermont PJ. 2005. Smooth muscle cell expression of a constitutive active form of human Rac 1 accelerates cutaneous wound repair. Surgery 137(1):92-101. [PubMed: 15614286]  [MGI Ref ID J:150480]

Ma Q; Cavallin LE; Yan B; Zhu S; Duran EM; Wang H; Hale LP; Dong C; Cesarman E; Mesri EA; Goldschmidt-Clermont PJ. 2009. Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. Proc Natl Acad Sci U S A 106(21):8683-8. [PubMed: 19429708]  [MGI Ref ID J:150015]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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