Ectopic growth of hippocampal mossy fibers in a mutated GAP-43 transgenic mouse with impaired spatial memory retention.
In a previous study, it was shown that transgenic mice, designated G-NonP, forget the location of a water maze hidden platform when tested 7 days after the last training day (Holahan and Routtenberg (2008) Hippocampus 18:1099-1102). The memory loss in G-NonP mice might be related to altered hippocampal architecture suggested by the fact that in the rat, 7 days after water maze training, there is discernible mossy fiber (MF) growth (Holahan et al. (2006) Hippocampus 16:560-570; Rekart et al. (2007) Learn Mem 14:416-421). In the present report, we studied the distribution of the MF system within the hippocampus of naïve, untrained, G-NonP mouse. In WT mice, the MF projection was restricted to the stratum lucidum of CA3 with no detectable MF innervation in distal stratum oriens (dSO). In G-NonP mice, in contrast, there was an ectopic projection terminating in the CA3 dSO. Unexpectedly, there was nearly a complete loss of immunostaining for the axonal marker Tau1 in the G-NonP transgenic mice in the MF terminal fields indicating that transgenesis itself leads to off-target consequences (Routtenberg (1996) Trends Neurosci 19:471-472). Because transgenic mice overexpressing nonmutated, wild type GAP-43 do not show this ectopic growth (Rekart et al., in press) and the G-NonP mice overexpress a mutated form of GAP-43 precluding its phosphorylation by protein kinase C (PKC), the possibility exists that permanently dephosphorylated GAP-43 disrupts normal axonal fasciculation which gives rise to the ectopic growth into dSO.
Holahan
Matthew R
MR
Department of Psychology, Institute of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada. matthew_holahan@carleton.ca
Honegger
Kyle S
KS
Routtenberg
Aryeh
A
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D056654:CA3 Region, Hippocampal / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D002645:Chickens; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013028:Space Perception
D019922:GAP-43 Protein; D012333:RNA, Messenger