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Publication : Behavioral and neurological analyses of adult mice carrying null and distinct loss-of-receptor function mutations in protein tyrosine phosphatase receptor type Z (PTPRZ).

First Author  Tanga N Year  2019
Journal  PLoS One Volume  14
Issue  6 Pages  e0217880
PubMed ID  31194769 Mgi Jnum  J:276448
Mgi Id  MGI:6314920 Doi  10.1371/journal.pone.0217880
Citation  Tanga N, et al. (2019) Behavioral and neurological analyses of adult mice carrying null and distinct loss-of-receptor function mutations in protein tyrosine phosphatase receptor type Z (PTPRZ). PLoS One 14(6):e0217880
abstractText  Protein tyrosine phosphatase receptor type Z (PTPRZ) is preferentially expressed in the central nervous system as two transmembrane receptor isoforms PTPRZ-A/B and one secretory isoform PTPRZ-S. Ptprz-knockout mice lacking the expression of all three isoforms show behavioral, learning, and neurological abnormalities, including increased exploratory activities to novelty, deficits in spatial and contextual learning, and reduced responses to methamphetamine, relative to wild-type mice. To investigate whether PTPRZ isoforms play distinct physiological roles, we herein performed behavioral studies on two knock-in mouse lines: One expresses the catalytically inactive Cys-1930 to Ser (CS) mutants of PTPRZ-A/B, while the other generated in the present study expresses catalytically active mutants of PTPRZ-A/B lacking the negative regulatory PTP-D2 domain and C-terminal PDZ-binding motif (DeltaD2) instead of wild-type PTPRZ-A/-B. In contrast to Ptprz-knockout mice, neither increased responses to novelty in the open field nor memory impairments in the inhibitory-avoidance task were observed in Ptprz-CS or Ptprz-DeltaD2 mice. However, the effects of methamphetamine on locomotor activity were significantly weaker in Ptprz-KO mice and CS mutant mice than in wild-type mice, but were normal in DeltaD2 mutant mice. Furthermore, microdialysis experiments revealed that methamphetamine-evoked dopamine release in the nucleus accumbens was reduced in Ptprz-KO mice and CS mutant mice. These results suggest that the extracellular region of PTPRZ, including the secretory isoform, is crucial for behavioral responses to novelty and the formation of aversive memories, whereas the PTPase activities of PTPRZ receptor isoforms are involved in regulating the dopaminergic system.
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