This is due to a mechanism of cross-resistance between pyrethroids and DDT, the so-called sodium channel mutation affecting neuronal signal transmission, which is governed by the kdr (knock-down resistance) gene (Martinez-Torres et al. 1998).
However, axonal degeneration in these same Plp1tg mice has been previously described (Anderson et al., 1998), indicating that the PLP mutation affects neuronal function.
Mutations affecting classical neuronal guidance cues (Netrin, Semaphorin, Slit/Robo, Ephrin) or adhesion molecules (cadherin, IgCAM) had, at best, weak effects on the M1 axon.
The mutations thus disturb the subtle equilibrium between cytoskeletal assembly and disassembly affecting neuronal plasticity and axonal transport across the microtubules.
Families with missense or splice site mutations affecting exon 10 have neuronal and glial inclusions while families with mutations outside of exon 10 have neuronal inclusions only, comprised of all six isoforms (Grover et al., 1999).
At present, the manner in which the dominant mutations in SPT1 affect neuronal function, particularly in peripheral nerves, is unclear.
Finally, a genetic screen for M1-defective phenotypes identified nine mutations for M1 development, including a mutation that may affect neuronal differentiation or cell fate specification.
However, for the ES cell cybrid CY3-I, carrying two mtDNA mutations affecting complex I activity, only 21% of cells showed neuronal development, compared with 53% in the parental ES cell line ES-I (P = 0.0013).
