Phenotypes Associated with This Genotype

Genotype
MGI:6281683

• Allelic Composition: Dnajc30^{tm1(KOMP)Vlcg}/Dnajc30^{tm1(KOMP)Vlcg}; Tg(Thy1-YFP)HJrs/0
• Genetic Background: involves: C57BL/6J * C57BL/6N
• Cell Lines: 16795A-A9

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

decreased corpus callosum size ( J:266469 )

• the ratio of corpus callosum:neocortex (CC:NCX) is disproportionately lower than that in wild-type controls

• the g-ratio (axon perimeter/axon+myelin perimeter) is significantly reduced, indicating decreased callosal axon thickness

abnormal cerebral cortex pyramidal cell morphology ( J:266469 )

• L5 neocortical pyramidal neurons (PNs) exhibit significantly reduced soma size

abnormal axon morphology ( J:266469 )

• EM analysis of transected corpus callosa revealed that the g-ratio (axon perimeter/axon+myelin perimeter) is significantly reduced, indicating smaller axon calibers

abnormal neuron physiology ( J:266469 )

• perforated patch recordings on neocortical pyramidal neurons revealed that the resting membrane potential is significantly more negative than that in wild-type neurons, consistent with lower intracellular ATP levels

• following treatment with tolbutamide (a K⁺_ATP channel inhibitor), pyramidal neurons fail to exhibit a more positive membrane potential, unlike in wild-type neurons

• following treatment with sodium azide (NaN₃), a complex IV inhibitor that indirectly decreases ATP, pyramidal neurons fail to exhibit a significant decrease in membrane potential, unlike in wild-type neurons

cellular

abnormal mitochondrial morphology ( J:266469 )

• EM analysis of L5 neocortical pyramidal neurons revealed an increase in mitochondrial density and a more rounded shape, consistent with increased mitochondrial fission

• however, cumulative mitochondrial coverage, area, and perimeter remain normal

abnormal mitochondrial shape ( J:266469 )

• L5 neocortical pyramidal neurons exhibit a more rounded mitochondrial shape (decreased aspect ratio)

increased mitochondrial number ( J:266469 )

• L5 neocortical pyramidal neurons exhibit an increase in mitochondrial density

abnormal mitochondrial physiology ( J:266469 )

• isolated neocortical mitochondria exhibit reduced ATP production in a luciferase-based ATP synthesis assay

• however, mitochondrial membrane potential and reactive oxygen species (ROS) production are normal

increased mitochondrial fission ( J:266469 )

• L5 neocortical pyramidal neurons exhibit dysmorphic mitochondria typical of increased mitochondrial fission

homeostasis/metabolism

decreased oxygen consumption ( J:266469 )

• cultured primary neocortical neurons show a significant reduction in basal oxygen consumption rate (OCR) relative to wild-type neurons

• following FCCP treatment to maximize mitochondrial respiration, primary neocortical neurons cannot respire at as high of a rate as wild-type neurons

• however, no differences in OCR are observed in response to oligomycin or antimycinA/rotenone treatment (OXPHOS-inhibiting drugs)