These mice carry the Gbatm1.1Mjff allele and the Tg(Thy1-SNCA)15Mjff transgene. They have applications related to Parkinson's disease, Gaucher disease and synucleinopathies, and neurodegeneration elicited by the aggregation of SNCA.
Kuldip Dave, The Michael J. Fox Foundation
Genetic Background | Generation |
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F10
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Humanized sequence, Not Specified) | Gba | glucosidase, beta, acid |
Starting at:
$278.00 Domestic price for female |
556.00 Domestic price for breeder pair |
Mutations in human GBA (glucosidase, beta, acid) can cause Gaucher disease, an autosomal recessive lysosomal (lipid) storage disease, and have been associated with late onset Parkinson's disease and Lewy body dementia.
These mice express a transgene containing human SNCA under the direction of a mouse Thy-1 promoter, and the mutant D427V GBA protein, which corresponds to the D409V mutation in the mature GBA protein. In addition, these mice possess loxP sites flanking exons 6 through 8 of the Gba gene.
When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 6 through 8 deleted in the cre-expressing tissues and will no longer express the mutant D427V protein.
Mice that are heterozygous for the Gbatm1.1Mjff allele and hemizygous for the Tg(Thy1-SNCA)15Mjff transgene are viable and fertile. Homozygous fertility for the Gbatm1.1Mjff allele or transgene has not been tested (June, 2016). As the mice are characterized, we will modify the strain description and add phenotype data.
Mice carrying the Gbatm1.1Mjff allele were bred to mice carrying the Tg(Thy1-SNCA)15Mjff transgene to generate this double mutant line.
For the Gbatm1.1Mjff allele, a targeting vector containing a FRT site flanked NEO cassette, and a F3 FRT site flanked PurO cassette was used to introduce the D427V point mutation into exon 10. The FRT site flanked NEO cassette was inserted into intron 5 and the F3 FRT site flanked PurO cassette was inserted into intron 8. In addition, loxP sites were inserted to flank exons 6 through 8. The construct was electroporated into C57BL/6NTac derived Art B6 3.6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were crossed to FLP recombinase expressing females on the C57BL/6NTac background, C57BL/6NTac-Tg(CAG-Flpe)2Art, to remove the selection cassettes. These mice no longer carry the FLP recombinase allele. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6N (Stock No. 005304) at least once to establish the colony.
The mThy1-hSNCA transgene consists of the human a-synuclein (SNCA) gene driven by a mouse thymus cell antigen 1 (Thy-1) promoter. The construct was microinjected into fertilized C57BL/6NTac oocytes and males from founder line 15 were bred to C57BL/6NTac females to establish the colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation.
Expressed Gene | SNCA, synuclein alpha, human |
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Site of Expression | |
Site of Expression |
Allele Name | transgene insertion 15, The Michael J Fox Foundation |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Tg(Thy1-SNCA)15Youy; Thy-1-SNCA |
Gene Symbol and Name | Tg(Thy1-SNCA)15Mjff, transgene insertion 15, The Michael J Fox Foundation |
Gene Synonym(s) | |
Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory |
Expressed Gene | SNCA, synuclein alpha, human |
Strain of Origin | C57BL/6NTac |
Chromosome | 11 |
Molecular Note | The transgene consists of the human alpha-synuclein (SNCA) gene driven by a mouse thymus cell antigen 1 (Thy-1) promoter. Line 15 was generated. Transgene insertion occurred on Chr 11, causing a 38 Kb deletion. |
Mutations Made By | Yingbin Ouyang, Taconic |
Allele Name | targeted mutation 1.1, The Michael J Fox Foundation |
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Allele Type | Targeted (Humanized sequence, Not Specified) |
Allele Synonym(s) | Gbatm1(D427V)Mjff; Gba1D409V |
Gene Symbol and Name | Gba, glucosidase, beta, acid |
Gene Synonym(s) | |
Promoter | Gba, glucosidase, beta, acid, mouse, laboratory |
Strain of Origin | C57BL/6NTac |
Chromosome | 3 |
Molecular Note | A targeting vector containing a FRT site flanked NEO cassette, and a F3 FRT site flanked PurO cassette was used to introduce the D427V point mutation into exon 10. D427V corresponds to the human D409V mutation. The FRT site flanked NEO cassette was inserted into intron 5 and the F3 FRT site flanked PurO cassette was inserted into intron 8. In addition, loxP sites were inserted to flank exons 6 through 8. Flp-mediated recombination removed the neo cassette. |
When maintaining a live colony, these mice can be bred as heterozygous for the Gbatm1.1Mjff allele and hemizygous for the Tg(Thy1-SNCA)15Mjff transgene. Homozygous fertility for the Gbatm1.1Mjff allele or transgene has not been tested (June, 2016).
When using the C57BL/6N-Gbatm1.1Mjff Tg(Thy1-SNCA)15Mjff/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #029124 in your Materials and Methods section.
Service/Product | Description | Price |
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Heterozygous for Gba<tm1.1Mjff> and Hemizygous or non-carrier for Tg(Thy1-SNCA)15Mjff |
Frozen Mouse Embryo | C57BL/6N-Gba<tm1.1Mjff> Tg(Thy1-SNCA)15Mjff/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6N-Gba<tm1.1Mjff> Tg(Thy1-SNCA)15Mjff/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6N-Gba<tm1.1Mjff> Tg(Thy1-SNCA)15Mjff/J | $3373.50 |
Frozen Mouse Embryo | C57BL/6N-Gba<tm1.1Mjff> Tg(Thy1-SNCA)15Mjff/J | $3373.50 |
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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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