| First Author | Flores B | Year | 2021 |
| Journal | Am J Physiol Cell Physiol | Volume | 320 |
| Issue | 5 | Pages | C722-C730 |
| PubMed ID | 33596149 | Mgi Jnum | J:316799 |
| Mgi Id | MGI:6514203 | Doi | 10.1152/ajpcell.00594.2020 |
| Citation | Flores B, et al. (2021) Temporal manipulation of KCC3 expression in juvenile or adult mice suggests irreversible developmental deficit in HSMN/ACC. Am J Physiol Cell Physiol |
| abstractText | Hereditary motor sensory neuropathy (HMSN/ACC) with Agenesis of the Corpus Callosum (ACC) has been documented in the French-derived populations of Charlevoix and Saguenay/Lac St. Jean in Quebec, Canada, as well as a few sporadic families throughout the world. HMSN/ACC occurs because of loss-of-function mutations in the potassium-chloride cotransporter 3, KCC3. In HMSN/ACC, motor deficits occur early in infancy with rapid and continual deterioration of motor and sensory fibers into juvenile and adulthood. Genetic work in mice has demonstrated that the disease is caused by loss of KCC3 function in neurons and particularly parvalbumin (PV)-expressing neurons. Currently, there are no treatments or cures for HMSN/ACC other than pain management. As genetic counseling in Quebec has increased as a preventative strategy, most individuals with HSMN/ACC are now adults. The onset of the disease is unknown. In particular, it is unknown if the disease starts early during development and whether it can be reversed by restoring KCC3 function. In this study, we used two separate mouse models, which when combined to the PV-Cre(ERT2) tamoxifen inducible system, allowed us to 1) disrupt KCC3 expression in adulthood or juvenile periods; and 2) re-introduce KCC3 expression in mice that first develop with a non-functional cotransporter. We show that disrupting or re-introducing KCC3 in the adult mouse has no effect on locomotor behavior, indicating that expression of KCC3 is critical during embryonic development and/or the perinatal period and that once the disease has started, re-expressing a functional cotransporter fails to change the course of HMSN/ACC. |
