A floxed STOP cassette disrupts exon 1 of the Gls gene in this strain. Homozygotes exhibit abnormal goal-directed behavior, die within 36 hours of birth. These mice may have application in studies related to cellular energy metabolism.
Stephen Rayport, Columbia University and NYSPI
Mariia Yuneva, University of California at San Francisco
Glutaminase is involved in glutamate neurotransmitter recycling, nitrogen metabolism, glycolysis in the presence of oxygen (Warburg effect) and regulation of reactive oxygen species.
These mice carry a floxed STOP cassette that disrupts exon 1, and when bred to mice that express Cre recombinase, resulting offspring will exhibit expression of Gls in cre-expressing tissues.
In the absence of recombination, the targeted mutation is a null allele and homozygotes die within the first postnatal day due to respiratory distress. Homozygotes are slightly smaller at birth than controls. Mice that are heterozygous for the targeted mutation are viable and fertile. No gene product (mRNA or protein) is detected by QRT-PCR analysis of fetal and adult tissue and Western blot analysis of brain tissue.
No enzymatic activity is detected in neonatal brain, kidney, and liver tissues from homozygotes.
Although neonate homozygotes are able to suckle, they do not feed and exhibit behavioral defects in their orientation to their mothers. Homozygous neonates spend a reduced amount of time supine and have decreased vocalization and locomotion under the dam's ventrum. Glutamatergic synaptic transmission is normal at baseline, but is diminished at physiological activation levels.
A PGK-NEO/STOP sequence cassette, flanked by loxP sites, was used to disrupt exon 1, preventing the transcription of Gls. The construct, generated by Dr. Stephen Rayport, while at Columbia University, was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were crossed to unknown genetic backgrounds. 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, Stephen Rayport|
|Allele Type||Targeted (Conditional ready (e.g. floxed), Null/Knockout)|
|Gene Symbol and Name||Gls, glutaminase|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||Floxed stop cassette was inserted by homologous recombination in Exon 1 preceding the ATG. Crossing these mice with tissue-specific cre expressors allows for tissue-specific rescue. Immumohistochemistry, Western, and QRT-PCR confirmed the absence of translation and transcription.|
When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes die within the first postnatal day due to respiratory distress.
When using the GLS null , GLS1 null mouse strain in a publication, please cite the originating article(s) and include JAX stock #017956 in your Materials and Methods section.
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