| First Author | Cerpa V | Year | 2014 |
| Journal | Neuroscience | Volume | 279 |
| Pages | 65-76 | PubMed ID | 25171790 |
| Mgi Jnum | J:215902 | Mgi Id | MGI:5607337 |
| Doi | 10.1016/j.neuroscience.2014.08.018 | Citation | Cerpa V, et al. (2014) Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception. Neuroscience 279:65-76 |
| abstractText | In genetically-modified Lmx1b(f/f/p) mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2-35mug of diphtheria toxin (DT) reduced the number of tryptophan hydroxylase-immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on minute ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24 degrees C, all Pet1/DTR mice dropped their body temperature (TB) below 35 degrees C after DT treatment, but the latency was shorter in males than females (3.0+/-0.37 vs. 4.57+/-0.29days, respectively; p<0.001). One week after DT treatment, mice were challenged by dropping TA from 37 degrees C to 24 degrees C, which caused TB to decrease more in males than in females (29.7+/-0.31 degrees C vs. 33.0+/-1.3 degrees C, p<0.01). We conclude that the 20% of 5-HT neurons that remain after DT treatment in Pet1/DTR mice are sufficient to maintain normal baseline breathing and a normal response to CO2, while those affected include some essential for thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. |
