Human ALFY knock-in mice for studying neurodegenerative disease

This technology is a conditional human ALFY protein-expressing mouse model for the study of diseases driven by pathological protein aggregation in the nervous system. ## Unmet Need: In vivo model that permits tissue-specific control of human ALFY expression Recent human genetic and experimental data suggest autophagy-linked FYVE protein (ALFY) overexpression as a promising disease-modifying strategy for Huntington’s disease and related proteinopathies. Although there is strong genetic evidence for its utility, there are currently no in vivo models that permit tissue-specific control of hALFY expression. ## The Technology: hALFY knock-in mouse model with LoxP-mediated expression control This technology is a hALFY knock-in mouse model that permits the localized study of hALFY expression via tissue-specific delivery of Cre recombinase, which excises a floxed stop cassette at the Rosa26 locus. Expression at this locus supports predictable, ubiquitous, controllable transgene expression without disrupting endogenous gene function. This model can be used to test hALFY overexpression for clearing pathological protein aggregation in the context of neurodegenerative diseases such as Huntington’s disease. This technology has been validated in vivo using several proteinopathy models, including those for Huntington’s disease. ## Applications: * Screening platform for hALFY-targeted therapeutics * Research model for dissecting the role of ALFY/WDFY3 in selective autophagy, CNS dysfunction, and neurodegenerative diseases (e.g., Huntington’s, Parkinson’s, etc.) * Preclinical regulatory testing model ## Advantages: * Enables precision hALFY expression in vivo via floxed stop codon * Rosa26 localization avoids positional effects and copy-number variability * Easy to interpret and reproducible phenotypes * Enables gain-of-function hALFY study when crossed with other disease models * FLAG tag enables highly sensitive, versatile detection and purification of hALFY ## Lead Inventor: [Ai Yamamoto, Ph.D.](https://www.neurology.columbia.edu/profile/ai-yamamoto-phd) ## Related Publications: * [Croce KR, Ng C, Pankiv S, Albarran E, Langfelder P, Ramos de Jesus A, et al. “A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy.” Neuron. 2025 Nov 19;113(22):3780-3797.e7.](https://pubmed.ncbi.nlm.nih.gov/40945514/) ## Tech Ventures Reference: * IR CU26143 * Licensing Contact: [Kristin Neuman](mailto:techtransfer@columbia.edu)