A stuttering-associated Gnptab variant alters fine-motor kinematics
Bishop, D.; Wang, S.; SheikhBahaei, S.
Show abstract
Precise reach-to-grasp movements rely on complex cortico-basal ganglia and cerebellar circuits, and can be affected by cellular pathway defects. We investigated whether mild Gnptab deficiency, affecting mannose-6-phosphate-dependent lysosomal enzyme targeting, impairs fine motor behaviors in mice. Using the staircase test, high-frame-rate video, and markerless tracking, we assessed reaching and grasping in Gnptab-mutant and control littermates. Our data suggest that Gnptab-mutant mice retrieved about 75% fewer pellets than controls and exhibited abnormal grasping, characterized by increased wrist extension and larger digit angles, decreased digital velocity, and shorter reach distances, while elbow angles remained largely unchanged. These findings suggest a specific deficit in grasp shaping and trajectory control, rather than overall limb positioning. Our data establishes a quantitative link between GNPTAB-related lysosomal pathway disruption and fine-motor impairments, providing a valuable model for understanding how cellular dysfunction impacts motor circuit function.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Quantification Of Mouse Reach Kinematics As A Foundation For Mechanistic Interrogation Of Motor Control 92%
- Selective loss of the GABAAα1 subunit from Purkinje cells is sufficient to induce a tremor phenotype 90%
- Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits 90%
Similar papers in this journal
- A novel, ataxic mouse model of Ataxia Telangiectasia caused by a clinically relevant nonsense mutation 93%
- TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons 93%
- Acute cerebellar knockdown of Sgce reproduces salient features of Myoclonus-dystonia (DYT11) in mice 93%
Similar papers in this journal
Similar papers in this journal
- Multidimensional analysis of a social behavior identifies regression and phenotypic heterogeneity in a female mouse model for Rett syndrome 94%
- Loss of Piccolo function in rats induces Pontocerebellar Hypoplasia type 3-like phenotypes 92%
- Impaired refinement of kinematic variability in Huntington disease mice on an automated home-cage forelimb motor task 92%