Advantages:
- Cell and Stage-specific Cre-loxP mediated ablation of Hs3st1/4/5
- First-ever floxed alleles for Hs3st4 and Hs3st5
- Captures complex neurological and behavioral phenotypes
- Evaluates drugs on HS pathways and 3-O-sulfation dependent motifs
Summary:
Heparan sulfate (HS) is a polysaccharide which plays a vital role in various biological processes including cell signaling, development, and neurodegeneration; 3-O sulfation is a modification in HS biosynthesis that critically regulates growth factor, morphogen, and neuronal signaling; however, it is difficult to study. Existing animal models either delete all HS 3-O sulfotransferases or lack knockouts for Hs3st4 and Hs3st5 entirely. This prevents researchers from distinguishing each isoform’s tissue and stage specific roles, identifying pathway-selective modulators, and/or linking HS structures to therapeutic outcomes.
Our researchers have engineered three floxed mouse lines—Hs3st1, Hs3st4, and Hs3st5—each flanked by loxP sites around an essential exon. By applying tissue- or time-specific Cre recombinase, researchers achieve spatiotemporally controlled ablation of individual Hs3st enzymes. These models facilitate the discovery of the roles of individual 3-O sulfotransferases in HS-dependent signaling pathways, structure-function analyses of 3-O sulfation, and in vivo screens for pathway-specific modulators, thereby addressing the unmet need for precise, isoform-specific tools to study HS biology and targeted therapeutic development.
Desired Partnerships: