Calca-flox Mouse

Calca, which encodes the neuropeptide calcitonin gene-related peptide (CGRP), is involved in multiple biological functions. It is expressed in a sub-population of glutamatergic neurons in the parabrachial nucleus (PBN) and plays a role in relaying aversive sensory information. It is associated with nociplasticity, a poorly understood phenomenon mediated by central nervous system plasticity [1,2,3].

In mouse models, preventing PBN Calca neurons from releasing neurotransmitters demonstrated that activation of these neurons is necessary for the manifestation and maintenance of chronic pain. Directly stimulating Calca neurons showed that their activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities can drive nociplasticity in a Calca-neuron-dependent manner. Also, chemogenetically inhibiting Calca neurons during CS1-CS2 pairing attenuated second-order conditioning, suggesting their role in associative learning [1,2,3]. In post-traumatic osteoarthritis mouse models, CALCA-/-mice had increased cartilage degeneration and subchondral bone loss, while osteophyte formation was reduced compared to wild-type mice, indicating the gene's role in osteoarthritis progression [4].

In conclusion, Calca is crucial for functions related to pain perception, associative learning, and osteoarthritis progression. The use of gene knockout mouse models has significantly enhanced our understanding of Calca's role in these biological processes and disease conditions, providing potential targets for treating chronic pain and osteoarthritis.