Sgta-/- mice lack exons 4-5 of the Sgta gene making this strain useful for studying the role played by SGTA in many vital processes (cell cycle regulation, apoptosis and others)
Wayne Tilley, The University of Adelaide
Sgta-/- mice lack exons 4-5 of the small glutamine rich tetratricopeptide repeat containing alpha (Sgta) gene. SGTA is a co-chaperone and regulator of androgen and growth hormone receptor signaling. It has been shown to be associated with cell cycle and apoptosis, viral assembly and release, hormone signaling, intracellular compartmentalization, neuronal synaptic transmission and the post-translational transport and modification of proteins. SGTA has also been linked to many cancers including prostate, ovary, liver and oesophagus cancer, as well as hormone-related polycystic ovary syndrome and amyloid-related Alzheimer’s and prion diseases. Homozygotes are viable but sub-fertile, having small litters and higher neonatal death rates. Pups are more susceptible to stillbirth, and are more prone to neonatal death between P2-P21. Less mice survive to weaning. Homozygotes are smaller than heterozygotes. There are very subtle effects of SGTA deficiency on the male reproductive system, including testis descent and organ size.
A targeting vector was designed to insert a loxP upstream of exon 4 (containing the start codon), and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of exon 5 of the small glutamine rich tetratricopeptide repeat containing alpha (Sgta) gene. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with C57BL/6 females. Resulting Sgtawt/flox offspring were bred to OzCre mice, expressing Cre Recombinase from the Gt(ROSA)26Sor locus on a C57BL/6 background, to remove the floxed sequence and the neo cassette. Resulting mice were crossed to C57BL/6 mice to remove the cre gene, and Sgta+/- mice were backcrossed to C57BL/6 mice for at least 12 generations (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1.1, Dame Roma Mitchell Cancer Research|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Sgta, small glutamine-rich tetratricopeptide repeat (TPR)-containing, alpha|
|Strain of Origin||C57BL/6|
|Molecular Note||A targeting vector was designed to insert a loxP upstream of exon 4 (containing the start codon), and an FRT-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of exon 5 gene. Cre-mediated recombination removed exons 4 through 5 and the neo cassette. Western blot and immunohistochemistry of prostrate and ovary confirmed that no protein was expressed in mutant mice.|
When maintaining a live colony, heterozygous mice may be bred together. Homozygotes are viable but sub-fertile.
When using the Sgta- mouse strain in a publication, please cite the originating article(s) and include JAX stock #029290 in your Materials and Methods section.
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