KIF1A.ORG’s 20th Research Roundtable meeting, “Investigation of Kif1a mouse models and therapeutic interventions,” was presented by Dr. Markus Terrey from The Jackson Laboratory (JAX). Read on to learn more about how JAX is creating animal models to better investigate and treat and KAND.
Attendance
26 RESEARCHERS, CLINICIANS, & BIOTECH REPS
21 RESEARCH INSTITUTIONS & INDUSTRY PARTNERS/ORGS
5 KIF1A.ORG REPS
Who Is Dr. Terrey?
Dr. Markus Terrey is an Associate Study Director in the Rare Disease Translational Center at JAX, where he researches neurodevelopmental and neurodegenerative disorders. The Lutz lab genetically engineers mice to model rare diseases, and has gone above and beyond in developing a suite of tools for KAND research, including mouse models and cell lines available for the KIF1A Research Network.
Summary
Main Takeaway
Having mouse models for KAND provides us with a huge leg up in our search for KAND treatments. Testing potential therapeutics in KIF1A mutant mice allows our Research Network to develop treatments and administration routes that are as effective and safe as possible.
Vocabulary
- Heterozygous: When an organism has one healthy and one mutant copy of a gene. In most cases, KAND is caused by a heterozygous mutation.
- Homozygous: When an organism has two mutant copies of a gene.
“Investigation of Kif1a mouse models and therapeutic interventions”
- Mouse mutations: JAX has multiple mouse lines carrying KIF1A mutations:
- L181F: This mutation hasn’t been observed in humans, but homozygous mice have symptoms associated with KAND, including leg paralysis and loss of long-range neuronal projections.
- P305L: This is a known mutation in our community. Homozygous mice with this mutation die shortly after birth, but heterozygous mice that better reflect P305L patients don’t have obvious symptoms.
- T99M: This is another severe disease mutation in our community, and JAX is currently developing this mouse line.
- Heterozygous mice: For each of these models, heterozygous mice, which genetically reflect most KAND cases, appear relatively healthy. The Lutz lab will investigate the behavior and cellular development of heterozygous mice for symptoms caused by mutant KIF1A.
- KIF1A overexpression: The Lutz Lab is generating a mouse line whose expression of healthy KIF1A can be increased at any age, which will teach us several things about KIF1A:
- Is overexpression of KIF1A in healthy mice well-tolerated, or harmful?
- Does overexpression of healthy KIF1A in mice with mutations treat their symptoms?
- What are the therapeutic windows for treating different symptoms of KAND?
- Prime-editing: In collaboration with Dr. David Liu at the Broad Institute, the Lutz Lab will investigate permanent gene editors to correct KIF1A mutations in their mouse lines. These tests will be invaluable for designing gene therapies that are as effective, specific, and safe as possible.
Together, these models are invaluable, and we’re grateful to Dr. Terrey, The Lutz Lab, and JAX for their partnership in our #relentless search for KAND treatments.