Selective Alteration of the Ventilatory Response to Hypoxia Results from Mutation in the Myelin Proteolipid Protein Gene

Mutation in the myelin proteolipid protein gene alters BK and SK channel function in the caudal medulla

“…The Mbp shi mouse has a mutation in the MBP gene, which results in CNS dysmyelination, however these mice do not exhibit seizures or early death as found in the rodents with Plp mutation. Furthermore, we have shown that the Mbp shi mouse has a normal ventilatory response to hypoxia (Miller et al 2004). …”

“…The response to 8% oxygen is characterized by an initial increase in ventilation over 1–2 min, followed by severe ventilatory depression terminating in apnea (Miller et al, 2003, 2004). This abnormality in ventilatory response to hypoxia develops between P18 and P21, the age at which seizures begin and early death occurs.…”

“…These rodents exhibit normal minute ventilation during sleep, and no apnea was observed. The defect in breathing control in these rodents is limited to the hypoxic ventilatory response, for the hypercapnic response is normal (Miller et al 2003, 2004). This finding suggests that the dysfunction in ventilatory response to hypoxia lies within the neuronal network which controls the response to hypoxia.…”

“…We compared whole-cell patch-clamp recordings of nTS neurons in in vitro brainstem slices in normal rodents, and rodents with three different mutations in the Plp gene—the myelin deficient (MD) rat, the myelin synthesis deficient ( Plp msd ) mouse, and the Plp null mouse—to determine whether Plp gene mutation alters the electrophysiological properties of neurons in the nTS and whether these effects occur at the same age at which lethal hypoxic ventilatory depression develops. In addition, in order to determine if dysmyelination alone could cause alteration of the electrophysiologic properties of neurons in the medulla, we studied the shiverer mouse ( Mbp shi ) which has dysmyelination due to a mutation in the myelin basic protein gene but no alteration in control of breathing (Miller et al 2004). …”

“… Proteolipid protein ( Plp ) gene mutation in rodents causes severe CNS dysmyelination, early death, and lethal hypoxic ventilatory depression (Miller et al 2004). To determine if Plp mutation alters neuronal function critical for control of breathing, the nucleus tractus solitarii (nTS) of four rodent strains were studied: myelin deficient rats (MD), myelin synthesis deficient ( Plp msd ), and Plp null mice, as well as shiverer ( Mbp shi ) mice, a myelin basic protein mutant.…”