Alb/SND1 mice use the mouse albumin promoter to direct expression of the human SND1 (staphylococcal nuclease and tudor domain containing 1) gene to hepatocytes. Hemizygous mice develop spontaneous hepatocellular carcinoma (HCC) with partial penetrance and an aggressive chemically-induced HCC. This strain may be useful in studies of the Snd1 oncogene and hepatocellular carcinoma.
Devanand Sarkar, Virginia Commonwealth University
The MYC and FLAG tagged Alb/SND1 transgene uses the mouse albumin enhancer/promoter to direct expression of the human SND1 (staphylococcal nuclease and tudor domain containing 1) gene to hepatocytes. SND1 encodes an endonuclease involved in the regulation of gene expression, including mRNA splicing, RNA editing and stability, as well as in the regulation of protein and lipid homeostasis. Overexpression of SND1 is associated with multiple cancers including hepatocellular carcinoma (HCC). SND1 may serve as a potential disease biomarker due to its positive correlation with cancer progression and metastatic spread. Hemizygous mice are viable and fertile. The donating investigator has not attempted to generate homozygous mice. By one year of age, approximately 42% of mice spontaneously develop HCC. In addition, the number spheroid-generating tumor-initiating cells (TIC) increase in size and number in transgenic hepatocytes. Administration of the chemical carcinogen, diethylnitrosamine (DEN), results in an aggressive HCC 32 weeks post-injection. This strain may be useful in studies of the Snd1 oncogene and hepatocellular carcinoma.
The Alb/SND1 transgene was designed with a 2.3 kb mouse albumin enhancer/promoter directing expression of the 2.7 kb human SND1 ORF (open reading frame) followed by C-terminal MYC and FLAG tags and a human polyA signal. The construct was microinjected into B6CBAF1 fertilized oocytes. Founder line 3a was determined to have the highest SND1 expression. The strain has been maintained through crosses to B6CBAF1 mice or non carriers from the colony. Upon arrival, mice were bred to B6CBAF1/J mice (Stock No. 100011) for at least one generation to establish the colony.
|Allele Name||transgene insertion 3a, Devanand Sarkar|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence, Epitope tag)|
|Gene Symbol and Name||Tg(Alb-SND1)3aDsar, transgene insertion 3a, Devanand Sarkar|
|Site of Expression||hepatocytes|
|Strain of Origin||(C57BL/6 x CBA)F1|
|Molecular Note||The C-terminal Myc- and FLAG-tagged human SND1 is under the control of an upstream enhancer region (-10400 to -8500) fused to the 335-bp core region of mouse albumin promoter. Western blot analysis confirmed expression of the protein in liver. Six lines were generated, with line 3a being the highest expressing line.|
When maintaining a live colony, hemizygous mice may be bred to wildtype mice from the colony. The donating investigator has not attempted to generate homozygous mice.
When using the Alb/SND1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #033355 in your Materials and Methods section.