Mouse Genome Informatics
hm1
    Nhlrc1tm1(KOMP)Vlcg/Nhlrc1tm1(KOMP)Vlcg
involves: C57BL/6J * C57BL/6NTac

cell line(s): 10571D-E2
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype

Lafora bodies in tissues of Nhlrc1tm1(KOMP)Vlcg/Nhlrc1tm1(KOMP)Vlcg mice

homeostasis/metabolism
• mice exhibit increased Lafora bodies and total glycogen levels in the heart muscle, skeletal muscle, and brain compared with wild-type mice (J:165994)
• brain glycogen levels in the insoluble pellet is increased compared to in wild-type mice (J:165994)
• however, no Lafora bodies are detected in the liver (J:165994)
• Laforin body inclusions increase in number and size with age and the accumulated glycogen is poorly branched compared to controls (J:218959)
• Laforin bodies accumulate in glial cells and neurons (J:218959)
• Laforin bodies are also seen in some fibers of skeletal muscle and heart (J:218959)

muscle
• Laforin bodies are also seen in some fibers of skeletal muscle and heart (J:218959)

behavior/neurological
• mice show spontaneous hippocampal seizures accompanied on occasion by myoclonus after a single injection of kainic acid unlike wild-type mice
• the presence of seizures reduces the amplitude and slope of fEPSPs evoked at the CA3-CA1 synapse
• train stimulation of Schaffer collaterals evokes long-lasting after-discharges in mutants but not wild-type mice
• mice are hyperactive at 11 months of age and show an increase in exploratory behavior, indicating reduced anxiety
• mice are hyperactive at 11 months of age and show an increase in exploratory behavior
• however, mice show normal gait and normal behavior in the rotarod or beam walking tests

nervous system
• mice show spontaneous hippocampal seizures accompanied on occasion by myoclonus after a single injection of kainic acid unlike wild-type mice
• the presence of seizures reduces the amplitude and slope of fEPSPs evoked at the CA3-CA1 synapse
• train stimulation of Schaffer collaterals evokes long-lasting after-discharges in mutants but not wild-type mice
• Laforin bodies are seen in several areas of the brain, most abundantly in the hippocampus and cerebellum, with glycogen-content increased 2-fold in whole brain of 11 month old mice
• Laforin bodies accumulate in glial cells by 11 months of age
• astrocytes often show Laforin bodies in their cytoplasm by 4 months of age
• 11 month old mice show an increase in GFAP+ cells in the hippocampus, indicating gliosis
• Laforin bodies accumulate in neurons by 11 months of age, in the neuronal somata of hippocampal PV+ interneurons and occasionally in their dendritic processes
• degeneration of PV+ interneurons in the hippocampus, with mice showing a reduction in the number of PV+ neurons at 11 months of age
• mice exhibit larger fEPSP amplitudes at higher stimulus intensities at the CA1 area, suggesting an enhanced synaptic excitability
• however, short-term plastic processes are not affected
• mice show larger and longer-lasting LTPs

Mouse Models of Human Disease
OMIM IDRef(s)
Myoclonic Epilepsy of Lafora 254780 J:165994 , J:218959