FINAL REPORT: Generation of mouse models of novel casein kinase 1δ (CKI δ ) migraine mutations

Summary

The aim of this study was to generate models of human mutations causing migraine with aura. Through two rounds of recombinations, the mutations (H46R and M59L) were introduced into the target regions. Detailed mappings were carried out for the modified BACs to ensure that correct constructs were obtained. Transgenic mice were then successfully generated.

Hypothesis vs. findings

Based on strong genetic evidence, we hypothesized that the CKIδ migraine mutations H46R and M59L are causative of migraine with aura. Thus we set out to generate mouse models of each so that they can be tested for evidence of migraine-related pathophysiology, such as altered thresholds for evoking cortical spreading depression and peripheral allodynia.

Unanswered Questions

Generating these mouse models is the first step toward probing the biology of migraine in families with CKIδ. Testing these mice in a number of assays will allow us to determine whether they represent good models of migraine-like pathology. If so, they will allow investigations into molecular details leading to headache in humans. Novel insights into migraine pain pathways may lead, ultimately, to new therapeutic approaches to headache.

What This Research Means To You

This work will allow us to pursue questions regarding how migraine occurs. This is necessary for the development of novel treatments for migraine and other forms of headache.