B6.129S4(Cg)-Tsc1^tm1Djk/MhnyJ

Stock number: 038428
Product name: Tsc1^c
Research areas: Cancer Research, Neurobiology Research, Research Tools

Description

These Tsc1^c floxed 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. Specifically on this congenic C57BL/6J background, mice are useful for creating a mouse model of chronic epilepsy.

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 and have no growth or behavioral defects. 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.

This congenic line is maintained on C57BL/6J genetic background, as compared with Stock No. 005680, which is maintained on a mixed genetic background. Mice from this congenic strain were bred to CMV-Cre mice (Stock No. 006054), with widespread Cre recombinase expression. The resulting heterozygous Tsc1^+/- mice were subsequently bred to BXD87/RwwJ mice (Stock No. 007130) to create a mouse model of chronic epilepsy. Half of the females from this cross suffer from chronic epilepsy.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

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. An aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664) to establish a live colony on a mixed genetic background as Stock No. 005680. Dr. Matt Mahoney acquired some of these mice while at University of Vermont and subsequently backcrossed them for six generations to C57BL/6J inbred mice to create this new congenic strain. Dr. Mahoney generously donated mice back to The Jackson Laboratory Repository to establish this congenic line as Stock No. 038428.

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.