These ENT-/- mice are deficient for Slc29a1 and exhibit decreased sensitivity to the effects of ethanol intoxication, decreased anxiety-like behavior and increased alcohol consumption. They have applications in studies related to alcohol dependence.
Doo-Sup Choi, Mayo Clinic
Slc29a1, also known as ENT1, encodes an ethanol sensitive sodium-independent equilibrative transporter of adenosine and regulates cellular adenosine concentrations. Adenosine acts as a neuromodulator and mediator of ethanol intoxication. Mice homozygous for this targeted mutation of Slc29a1 exhibit reduced behavioral effects of ethanol intoxication, increased alcohol consumption and decreased anxiety-like behavior when compared to wildtype controls.
No gene product (mRNA) is detected by in situ hybridization analysis of brain sections from homozygotes. No functional protein is detected by binding and uptake activity analysis. At 10-12 weeks of age, homozygotes have a smaller body weight than wildtype controls. Homozygotes display decreased ethanol-induced motor incoordination and righting reflex loss as well as an enhanced preference for ethanol. Adenosine A1 receptor function in the striatum is diminished. Increased frequency and amplitude of spontaneous
excitatory postsynaptic currents (EPSCs) and elevated glutamate levels in the nucleus accumbens are also observed. The flagellum of sperm from homozygotes have a slightly diminished response to accelerating stimuli (2-chloro-2'-deoxyadenosine).
Mice that are homozygous for the targeted mutation are viable, fertile, and normal in size.
A loxP site flanked targeting vector containing a PGK-NEO cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 4 of the targeted gene, and another loxP site was inserted upstream of exon 2. The construct was electroporated into unspecified 129X1/SvJ derived embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette or exons 2-4 were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6 for more than 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Robert O Messing|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Slc29a1tm1Msg; targeted mutation 1, Robert O Messing|
|Gene Symbol and Name||Slc29a1, solute carrier family 29 (nucleoside transporters), member 1|
|Gene Synonym(s)||ENT1; expressed sequence AA407560; rENT1; 1200014D21Rik; NBMPR-sensitive equilibrative nucleoside transporter; RIKEN cDNA 1200014D21 gene; AA407560; 1200014D21Rik|
|Strain of Origin||129X1/SvJ|
ES cell line derived from 129X1/SvJ
|Molecular Note||The targeting construct included exons 2-4 of the gene and a neomycin cassette flanked by loxP sequences. Clones were transfected with a Cre plasmid. ES cell lines showing a deletion of exons 2-4 and the neomycin cassette were selected for microinjection. The mutation was confirmed by PCR, Southern blot and in situ hybridization.|
|Mutations Made By|| |
Robert O. Messing, The University of Texas at Austin
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129X1-Slc29a1tm1Msg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017739 in your Materials and Methods section.
|Heterozygous or wildtype for Slc29a1<tm1Msg>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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