Rps6kb1 (S6K1) knock-out mice exhibit growth delays early in development and impaired glucose tolerance. They are suitable for use in applications related to the study of glucose homeostasis, energy metabolism and the mTORC1 signaling pathway.
Nahum Sonenberg, McGill University
The targeted Rps6kb1 gene encodes a serine/threonine kinase that is part of the PI3K/AKT/mTOR pathway. Expression of this gene and altered phosphorylation of S6K1 is been associated with human cancer. These S6K1 (also known as p70) knock-out mice carry an allele in which the sequence encoding the serine threonine kinase catalytic subdomains VIII–X was replaced with a neo cassette.
At E12.5 and E14.5, homozygous embryos can be up to 30% smaller in size than wild-type controls. Mice that are homozygous for the targeted mutation are viable and fertile. Homozygous mice exhibit growth retardation that becomes less significant in adulthood.
No gene product (protein) is detected by western blot analysis of thymus from homozygotes.
Pancreatic beta islet cells from homozygotes secrete less insulin and have reduced mass compared to wild-type controls. Knock-out mice have half the beta-cell mass of control animals and a 40 to 50% decrease in circulating insulin levels. After glucose challenge, homozygous mice exhibit impaired glucose tolerance with hyperglycemia.
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. 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.
A targeting vector containing a neo cassette was used to disrupt 1.2 kb of Rps6kb1 sequence encoding the serine threonine kinase catalytic subdomains VIII–X. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells.
Chimeric mice were generated by aggregating correctly targeted ES cells with (C57BL/6 x DBA/2) F1 morula-stage embryos.
The resulting chimeric animals were bred to C57BL/6 mice to achieve germline transmission. The mice were bred to 2 other targeted mutation (knock-out) strains on a C.129S4 background.
The mice were backcrossed to BALB/cAnNCrl for ten generations.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize BALB/cByJ oocytes (Stock No. 001026). The other targeted mutations were bred out of the line.
|Allele Name||targeted mutation 1, George Thomas|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, George Thomas; Rps6kb1tm1Gtho|
|Gene Symbol and Name||Rps6kb1, ribosomal protein S6 kinase, polypeptide 1|
|Gene Synonym(s)||expressed sequence AI256796; S6K1; expressed sequence AA959758; S6K; PS6K; AI256796; 2610318I15Rik; AA959758; AI314060; p70 S6KA; p70(S6K)-alpha; p70-alpha; p70-S6K; p70/85s6k; p70s6k; S6K-beta-1; expressed sequence AI314060; RIKEN cDNA 2610318I15 gene; STK14A; 2610318I15Rik; p70S6K1; p70 S6K-alpha|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||1.2 kb of genomic sequence, including regions encoding the conserved serine threonine kinase catalytic subdomains 8 through 10, was replaced with a neomycin selection cassette by homologous recombination. Western blot analysis of homozygous mutant mice using two antibodies directed to the amino and carboxy termini showed an absence of protein. A kinase phosphorylation assay showed no activity in homozygous mutant mice verifying a complete functional ablation.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the S6K1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #031508 in your Materials and Methods section.
|Heterozygous or wildtype for Rps6kb1<tm1Gtho>|
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