Fig. 2: Triple conditional Nrxn123 or PtprDFS 3cKO mice crossed with PV-Cre driver mice exhibit only minor motor impairments, whereas sextuple conditional Nrxn123-PtprDFS 6cKO mice crossed with PV-Cre driver mice display a severe motor phenotype.

a Breeding strategy. Triple Nrxn123 and PtprDFS cKO mice were crossed to PV-Cre mice and to each other to generate Nrxn123 3cKO/PV-Cre, PtprDFS 3cKO/PV-Cre, and sextuple Nrxn123-PtprDFS cKO/PV-Cre mice with littermate controls lacking PV-Cre that were used in all experiments. b Representative traces of locomotor activity of Nrxn123 triple cKO (left), PtprDFS triple cKO (middle), or Nrxn123, PtprDFS sextuple cKO (right) mice tested in the open field arena. c Quantification of the open field test and tremor behavior. Summary graphs show data for the distance travelled, and the time spend in the center of the arena. Graphs on the right illustrate the tremor behavior of mice, analyzed using 10 min force plate measurements44, 68. The tremor index was calculated by integrating the power in the 9-Hz to 12-Hz range. The averaged power in the 3-Hz to 6-Hz range was used as baseline. d Representative images from footprint analyses comparing the gait of PV-Cre- and PV-Cre+ littermates from Nrxn123 triple cKO (left), PtprDFS triple cKO (middle), or Nrxn123, PtprDFS sextuple cKO (right) mice. e PV-Cre+ sextuple cKO mice exhibit less accurate and uniform foot placement compared to PV-Cre-, as evidenced by an increase in the distance between the placement of the right forepaw and hindpaw, and left forepaw and hindpaw (forepaw/hindpaw overlap), as well as changes in the hindpaw footprint size. f, g Performance of littermate PV-Cre- and PV-Cre+ mice on the accelerating rotarod (4–40 rpm). Latency to fall and end speeds are plotted across trials. Summary graphs show initial coordination and learning rate confirming severe motor impairments in mice lacking both Nrxn123 and PtprDFS. All data in summary plots and summary graphs are means ± SEM. Statistical significance was assessed by two-tailed Mann-Whitney test for summary graphs, or two-way ANOVA for graphs in f, g. All graphs show independent replicates (n = mice). Source data and statistical results are provided within the Source Data file.