Anxa1-Cre mouse for selective modeling of dopaminergic neurons in Parkinson's disease

This technology is an Anxa1-Cre knock-in mouse line that provides specific genetic access to a subtype of dopaminergic neurons, enabling precise modeling of early Parkinson’s motor deficits.

Unmet Need: A specific model for early Parkinson's motor deficits

In Parkinson's disease, the degeneration of dopaminergic neurons is known to be heterogeneous; however, it is unclear whether a specific, molecularly defined subtype is uniquely vulnerable and responsible for driving the onset of motor symptoms. The lack of tools to functionally isolate and test the role of these specific cell populations makes it difficult to determine if their loss is simply a biomarker or a critical driver of early disease progression. Resolving this is critical for developing targeted therapies that can protect vulnerable neurons and potentially slow or halt the disease at its earliest stages.

The Technology: Mouse line for targeted manipulation of a key Parkinson's disease neuron subtype

This technology is a knock-in mouse line, created using CRISPR/Cas9 technology, in which the expression of Cre recombinase is driven by the endogenous promoter for the Anxa1 gene. The mouse expresses Cre specifically in Anxa1-positive cells. When crossed with mice containing floxed genes, this tool allows researchers to precisely manipulate the genes of interest—for expression, deletion, or functional modulation—exclusively within the Anxa1-expressing cell population. This enables the functional study of a specific subtype of dopaminergic neurons that has been identified as uniquely vulnerable in the progression of Parkinson's disease.

This mouse model has been validated in mice in the context of Parkinson's disease research.

Applications:

• In vivo platform for neurodegenerative therapeutics screening
• Target and mechanism validation
• Biomarker discovery
• Research tool for analysis of neural circuits driving early Parkinson’s disease motor symptoms
• Research tool to investigate the function, connectivity, and properties of Anxa1-expressing neurons

Advantages:

• High molecular specificity
• Model for functional causality of neuron subtype
• Model for early disease onset
• Versatile and easily shareable research platform

Lead Inventor:

Rui Costa, D.V.M., Ph.D.

Related Publications:

• Fushiki A, Ng D, Lewis ZR, Yadav A, Saraiva T, Hammond LA, Wirblich C, Tasic B, Menon V, Alves da Silva J, Costa RM. “A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson's Disease” bioRxiv. 2024 Dec 21.

Tech Ventures Reference:

• IR CU26032

• Licensing Contact: Kristin Neuman