Neuropilin-1 Sema Mice

Value Proposition:

• Extended Survival for Research: Unlike mice that completely lack Npn-1 and die early in development, these mice live until birth, making them more useful for studying how Npn-1 functions in living systems.
• Tool for Mechanistic Studies: The gene replacement strategy provides a unique model to dissect the roles of semaphorin vs. VEGF signaling in development and disease.
• Potential Therapeutic Insights: Understanding differential ligand binding may inform therapeutic strategies for diseases involving angiogenesis or neural development, such as cancer or neurodegeneration.
• Genetic Precision: The engineered mouse model offers a genetically precise system for studying receptor-ligand interactions without complete loss of receptor function.

Unmet Need:

Neuropilin-1 (Npn-1) is a receptor with essential functions in vascular and neuronal development through its interactions with ligand families including semaphorins (Sema) and vascular endothelial growth factors (VEGF). Complete knockout of Npn-1 results in early embryonic lethality, limiting its utility for studying post-embryonic functions in mouse studies. Therefore, there is a strong need for a transgenic mouse model that allows selective disruption of Npn-1 ligand interactions to better understand its role in development and disease without compromising viability.

Technology Description:

Researchers at Johns Hopkins have developed a genetically engineered mouse model, Npn-1Sema-, which expresses a modified form of Neuropilin-1 that retains VEGF binding but lacks semaphorin interaction. This model was created using a gene replacement strategy and allows for the study of Npn-1 function beyond early embryonic stages. The homozygous Npn-1Sema- mice survive until birth, unlike Npn-1 null mice, and serve as a powerful tool for dissecting the distinct roles of Npn-1 ligands in vascular and neuronal development.

Stage of Development:

• The Npn-1 Sema- mouse model has been successfully generated and characterized.
• Phenotypic analysis confirms survival to birth and selective ligand binding.

Data Availability:

• https://www.jax.org/strain/005245
• https://pubmed.ncbi.nlm.nih.gov/12852851/