This Tsc2-DN transgenic mouse strain expresses a dominant negative mutant mouse Tsc2 (tuberous sclerosis 2) may be useful in studies of tuberous sclerosis.
Jack L Arbiser, Emory University
These Delta RG transgenic mice express a dominant negative mutant mouse Tsc2 (tuberous sclerosis 2) gene that lacks the sequence encoding the rabaptin-5 and rap1GAP motifs. Expression is directed by the CMV, cytomegalovirus, promoter. TSC2 is a putative tumor supressor. Mutation of TSC2 have been associated with the onset of tuberous sclerosis complex (TSC) which is characterized by the formation of non-malignant tumors in many different organs.
Mice that are hemizygous for the transgene are viable and fertile. They develop skin and brain hamartomas with aggregates of granular cells at the surface cerebellum (subpial) and collagenous fibrovascular proliferations containing abundant mast cells in the skin. Hemizygotes exhibit higher anxiety, spending less time in the open arms of an elevated plus maze when compared to wildtype mice. Mild learning and memory defects are also observed.
The Δ-RG (DRG) transgenic construct containing mutant mouse Tsc2 (tuberous sclerosis 2) cDNA, lacking the sequence encoding the rabaptin-5 and rap1GAP motifs, under control of the CMV (cytomegalovirus) promoter was injected into fertilized C57BL/6 mouse eggs. The donating investigator reported that the resulting male transgenic mice were maintained on the C57BL/6 background (see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Expressed Gene||Tsc2, tuberous sclerosis 2, mouse, laboratory|
|Site of Expression|
|Allele Name||transgene insertion 1, Jack Arbiser|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Allele Synonym(s)||transgene insertion 1, Jack Arbiser; Tg(CMV-Tsc2*)1Arbi|
|Gene Symbol and Name||Tg(CMV-Tsc2*)1Arbi, transgene insertion 1, Jack Arbiser|
|Promoter||CMV, cytomegalovirus, human|
|Expressed Gene||Tsc2, tuberous sclerosis 2, mouse, laboratory|
|Strain of Origin||C57BL/6|
|Molecular Note||The delta-RG (DRG) transgenic construct contains a mutant mouse Tsc2 (tuberous sclerosis 2) cDNA, lacking the sequence encoding the rabaptin-5 and rap1GAP motifs, under control of the CMV (cytomegalovirus) promoter. Line 1 was generated.|
When maintaining a live colony, these mice can be bred as hemizygotes.
When using the C57BL/6-Tg(CMV-Tsc2*)1Arbi/KlanJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #014564 in your Materials and Methods section.
|Hemizygous or Non carrier for Tg(CMV-Tsc2*)1Arbi|
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