Value Proposition
· Genetically modified mouse model with targeted GFP knock-in to the Islr2/Linx locus, enabling real-time visualization of specific neuronal populations during critical developmental windows
· Dual functionality - the null mutation eliminates Linx protein to reveal functional defects (shorter, thinner nerves and stalled branching), while EGFP reporter visualizes which neurons normally express Linx and tracks their axonal projections in real-time
· Validated phenotype that recapitulates known neurotrophin signaling defects, providing a reliable model for studying sensory and motor neuron development
· GFP reporter provides spatial-temporal resolution for tracking axonal projections in live tissue, enabling dynamic studies of neural circuit formation
· Enables mechanistic studies of Linx interactions with multiple receptor tyrosine kinases (TrkA, TrkC, Ret, p75NTR) in a single model system
Unmet Need
Understanding peripheral nervous system development requires sophisticated tools to study how guidance molecules like Islr2 (Linx) coordinate with neurotrophin receptor signaling to establish neural circuits. Current approaches rely on separate knockout and reporter lines or in vitro systems that cannot fully capture the complexity of in vivo neurodevelopment. Existing models lack the ability to simultaneously assess gene function and visualize specific neuronal populations during circuit formation. Therefore, there is a strong need for integrated mouse models that combine functional gene disruption with real-time visualization capabilities to advance our understanding of neurodevelopmental mechanisms.
Technology Description
Researchers at Johns Hopkins have developed a genetically modified mouse strain that addresses critical gaps in peripheral nervous system research. The technology targets Islr2 (Linx), an immunoglobulin superfamily protein that regulates axon extension through interactions with neurotrophin receptors (TrkA, TrkC, Ret, p75NTR). A tau-EGFP reporter gene is inserted into the Islr2 locus, creating both a null mutation and fluorescent labeling of Linx-expressing neurons.
Stage of Development
· This technology is a tangible material (mouse strain) and as such can be marketed and licensed as a stand alone invention to interested parties. This mutant mouse strain is currently available on Jax Lab’s repository (as of 10/1/2025):
o Jax # 016607 B6.129S6(Cg)-Islr2tm1.1Ddg/J
Data Availability
· n/a
Publication
Mandai K, Guo T, St Hillaire C, Meabon JS, Kanning KC, Bothwell M, Ginty DD. LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development. Neuron. 2009 Sep 10;63(5):614-27. doi: 10.1016/j.neuron.2009.07.031. PMID: 19755105; PMCID: PMC2758028.
