FVB.129S1(Cg)-Slc2a1^tm1.1Stma/AbelJwkimJ

Stock number: 034622
Product name: FVB.Glut1^fl
Strain synonyms: Floxed Glut1 on FVB

Research areas: Cancer Research, Research Tools

Description

FVB.Glut1^fl floxed mutant mice possess loxP sites flanking exons 3 through 8 of the Slc2a1 gene. These mice are useful in studies of glucose metabolism, glycolysis in cancer cells, immune cells, and other Glut1 expressing cells.

Detailed description

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. The phenotype summarized below is for the parental line: Glut1^fl mice on a STOCK genetic background (Stock No. 031871). It should be noted that the phenotype of this FVB/NJ-congenic Glut1^fl line (Stock No. 034622) could vary from that of the parental line from which it was derived.

The targeted Slc2a1 (GLUT1) gene encodes a hexose transporter that is a major facilitative glucose transporter across the blood-brain barrier and in cancer cells. Mutations in this gene have been associated with Dystonia 9, GLUT1 Deficiency Syndrome, stomatin-deficient cryohydrocytosis with neurological defects, and early-onset absence epilepsy. These mice possess loxP sites flanking exons 3 through 8 of the enodgenous Slc2a1 gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3 through 8 deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele.

When bred to a strain with Cre recombinase expression in early double-negative thymocytes (see Stock No. 003802 for example), or with a strain with Cre recombinase expression in very late double-negative stage T cells (see Stock No. 017336 for example), this mutant mouse strain may be useful in studies of thymic development and T cell maturation.

Development

A targeting vector containing a frt-Neo-frt-loxP selection cassette was inserted downstream of exon 8 of the targeted gene, and another loxP site was inserted into intron 2. This construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were tested for germline transmission. Heterozygotes were crossed to transgenic mice with germline expression of FLPe recombinase (unknown genetic background) to excise the selection cassette, leaving exons 3 through 8 flanked by loxP sites.

In 2016, Dr. Jung-Whan Kim received some Glut1^fl animals (backcrossed onto a C57BL/6 genetic background) from Dr. E. Dale Abel at University of Iowa and then backcrossed them at least 15 generations to FVB/NJ inbred mice (from Stock No. 001800). The resulting FVB/NJ-congenic strain is called FVB.Glut1^fl. Of note, the donating investigator reports that, at least once during backcrossing, a Glut1^fl female was bred to an FVB/NJ inbred male (thus the Y chromosome of the congenic strain is of FVB/NJ origin). In 2020, FVB.Glut1^fl males (white coat color) were sent to The Jackson Laboratory Repository as Stock No. 034622. Upon arrival, males were used to cryopreserve sperm. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Slc2a1^tm1.1Stma
Name: targeted mutation 1.1, Steven M Anderson
MGI accession ID: MGI:5293720
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: GLUT1^fl
Marker symbol: Slc2a1
Marker name: solute carrier family 2 (facilitated glucose transporter), member 1
Marker synonyms: CSE; DYT17; DYT18; DYT9; EIG12; GLUT; GLUT1; Glut-1; GLUT1DS; GLUTB; GTG1; Gtg3; HTLVR; M100200; PED; RATGTG1; Rgsc200; SDCHCN
Chromosome: 4
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A loxP site was inserted upstream of exon 3. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 8. Flp-mediated recombination removed the neo cassette and left exons 3 through 8 floxed.