STOCK Tsc1^tm1Djk/J

Stock number: 005680
Product name: Tsc1^c
Strain synonyms: Tsc1 flox
Research areas: Research Tools

Description

These floxed mutant mice possess loxP sites flanking exons 17 and 18 of the Tsc1 gene. This mutant strain may be useful in tissue-specific studies including tuberous sclerosis or other hamartoma syndromes, regulation of the actin cytoskeleton and motility, cellular and organismal glucose homeostasis, cell growth responses, apoptosis regulation, and regulation of cell size.

This mutation is also available on a congenic C57BL/6J genetic background as Stock No. 038428.

Detailed description

These Tsc1^c floxed mice possess loxP sites flanking exons 17 and 18 of the TSC complex subunit 1 (Tsc1) gene. TSC1 is a tumor suppressor gene that encodes the growth inhibitory protein hamartin which interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex regulates anabolic cell growth by negatively regulating mTORC1 signaling. TSC1 also inhibits ATPase activity of Hsp90 and facilitates Hsp90-mediated ubiquitination and proteasomal degradation. Tsc1^c homozygous mice are viable and fertile, have no growth or behavioral defects, and are devoid of tumors through age 18 months. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 17-18 removed in the cre-expressing tissues of the offspring.

When bred to a strain expressing Cre recombinase in neuronal cells (see Stock No. 003966 for example), this mutant mouse strain may be useful in studies of tuberous sclerosis.

When bred to a strain expressing Cre recombinase in oocytes of the primordial follicles (see Stock No. 011062 for example), this mutant mouse strain may be useful in studies of primordial follicle quiescence and activation.

When bred to a strain expressing Cre recombinase in liver (see Stock No. 003574 for example), this mutant mouse strain may be useful in studies of hepatic lipid metabolism.

Importation of this model was supported by the Tuberous Sclerosis Alliance.

This mutation is also available on a congenic C57BL/6J genetic background as Stock No. 038428.

Development

The Tsc1^c targeting vector contains a loxP-flanked neomycin resistance-thymidine kinase gene cassette preceding exon 17 and a third loxP site downstream of exon 18 of the TSC complex subunit 1 (Tsc1) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were backcrossed for germ-line transmission to C57BL/6J, BALB/cJ, or 129/SvJae mice. The resulting heterozygotes were intercrossed to produce homozygotes on a mixed background. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664)

Allele

Symbol: Tsc1^tm1Djk
Name: targeted mutation 1, David J Kwiatkowski
MGI accession ID: MGI:2656240
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Tsc1^c; Tsc1^fl; Tsc1^flox; Tsc1^L; Tsc1^lox
Marker symbol: Tsc1
Marker name: tuberous sclerosis 1
Marker synonyms: hamartin; LAM; TSC; tuberous sclerosis 1
Chromosome: 2
Strain of origin: 129S4/SvJae
Molecular note: A floxed neo-TK cassette was inserted into the intron preceding exon 17 and a third loxP site was introduced downstream of exon 18 by homologous recombination.
General note: Phenotypic Similarity to Human Syndrome: Angiosarcoma/Lymphangiosarcoma J: 231316.