huSLC5A2 Mouse
Product Name
huSLC5A2 Mouse
Product ID
C002135
Strain Name
C57BL/6Cya-Slc5a2tm1(hSLC5A2)/Cya
Background
C57BL/6Cya
Status
Citations
0
When using this mouse strain in a publication, please cite “huSLC5A2 Mouse (Catalog C002135) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
SLC5A2
Gene Alias
SGLT2
NCBI ID
Chromosome
Chr 16 (Human)
MGI ID
Datasheet
Strain Description
The SLC5A2 gene, also known as SGLT2, encodes sodium-glucose cotransporter 2, a member of the solute carrier family 5 and a low-affinity, high-capacity sodium-glucose cotransporter. It is highly expressed in the brush border of the early segment (S1 segment) of the renal proximal tubule, where it is responsible for reabsorbing approximately 90% of glucose from the glomerular filtrate [1-2]. In glucose homeostasis, the SGLT2 protein prevents energy loss through urine by efficiently reabsorbing filtered glucose; inhibiting its function can directly induce glucosuria, thereby lowering blood glucose [3]. SGLT2 overexpression or enhanced activity is closely associated with the progression of type 2 diabetes, chronic kidney disease, and heart failure, making it an important therapeutic target: in type 2 diabetes, hyperglycemia leads to a significant increase in the glucose load filtered by the glomeruli, and the proximal tubule undergoes compensatory hypertrophy and hyperplasia, with SGLT2-mediated glucose and sodium reabsorptive capacity subsequently enhanced, thereby accelerating diabetic nephropathy progression [4]; in chronic kidney disease, single-nephron hyperfiltration in remnant nephrons further exacerbates the SGLT2-dependent reabsorptive burden, forming a vicious cycle [5]; in heart failure, increased volume load, sympathetic activation, and elevated angiotensin II can also upregulate SGLT2 activity, promoting proximal sodium reabsorption and aggravating fluid and sodium retention as well as cardiorenal burden [6]. Loss-of-function mutations in SLC5A2 cause familial renal glucosuria, characterized by persistent isolated glucosuria in the presence of normal blood glucose levels, generally with a favorable prognosis, but may be accompanied by varying degrees of sodium loss and volume changes [7]. In addition to improving glycemic control, SGLT2 inhibitors also exert weight reduction, blood pressure lowering, and significant cardiorenal protective effects [3,6].
The huSLC5A2 mouse is a humanized mouse model generated by gene editing, in which the sequence from exon 1 through part of intron 12 of the mouse Slc5a2 gene was replaced with the sequence from exon 1 through exon 14 of the human SLC5A2 gene, together with the SV40 late pA sequence. This model can be used for mechanistic studies of type 2 diabetes, chronic kidney disease, heart failure, familial renal glucosuria, and other related diseases, as well as for the screening, efficacy evaluation, and preclinical in vivo studies of small molecule inhibitors, antibodies, small nucleic acid drugs, and other therapeutics targeting human SGLT2.
Reference
Kanai Y, Lee WS, You G, et al. The human kidney low affinity Na⁺/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. Journal of Clinical Investigation. 1994;93:397-404.
Wells RG, Pajor AM, Kanai Y, et al. Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. American Journal of Physiology. 1992;263:F459-F465.
Vallon, Volker., Vallon, Volker., Vallon, Volker., Thomson, Scott C., & Thomson, Scott C.. (2016). Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia, 60(2), 215-225.
Vallon, Volker., Vallon, Volker., Vallon, Volker., Thomson, Scott C., & Thomson, Scott C.. (2020). The tubular hypothesis of nephron filtration and diabetic kidney disease. Nature reviews. Nephrology, 16(6), 317-336.
Vallon, Volker., Vallon, Volker., & Vallon, Volker.. (2024). State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications. American journal of hypertension.
Packer M. SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism. Nat Rev Cardiol. 2023;20(7):443-462.
Calado, J., Loeffler, J., Sakallioglu, O., Gok, F., & Lhotta, K.. (2006). Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney international, 69(5), 852-5.
Strain Strategy
The exon 1 to partial intron 12 of mouse Slc5a2 was replaced with the exon 1 to exon 14 of human SLC5A2 and SV40 late pA.
Figure 1. Gene editing strategy for huSLC5A2 mice.
Application Area
Mechanistic studies of related diseases such as type 2 diabetes, chronic kidney disease, heart failure, and familial renal glucosuria;
Screening, efficacy evaluation, and preclinical in vivo studies of drugs targeting human SGLT2, including small molecule inhibitors, antibodies, and small nucleic acid drugs.
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