Phenotypes Associated with This Genotype

Genotype
MGI:4839642

• Allelic Composition: Nhlrc1^{tm1(KOMP)Vlcg}/Nhlrc1^{tm1(KOMP)Vlcg}
• Genetic Background: involves: C57BL/6J * C57BL/6NTac
• Cell Lines: 10571D-E2

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

Lafora bodies in tissues of Nhlrc1^{tm1(KOMP)Vlcg}/Nhlrc1^{tm1(KOMP)Vlcg} mice

homeostasis/metabolism

increased glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in the heart muscle, skeletal muscle, and brain compared with wild-type mice

increased cardiac muscle glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in the heart muscle

increased brain glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in brain

• brain glycogen levels in the insoluble pellet is increased compared to in wild-type mice

increased skeletal muscle glycogen level ( J:165994 , J:218959 )

• mice exhibit increased total glycogen levels in skeletal muscle (J:165994)

muscle

increased cardiac muscle glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in the heart muscle

increased skeletal muscle glycogen level ( J:165994 , J:218959 )

• mice exhibit increased total glycogen levels in skeletal muscle (J:165994)

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:218959 )

• 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

decreased anxiety-related response ( J:218959 )

• mice are hyperactive at 11 months of age and show an increase in exploratory behavior, indicating reduced anxiety

hyperactivity ( J:218959 )

• 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

increased susceptibility to pharmacologically induced seizures ( J:218959 )

• 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

abnormal brain morphology ( J:216806 , J:218959 )

• at 16 months of age, mutant brains accumulate similar but larger and more abundant PAS- and muscle glycogen synthase (MGS)-positive polyglucosan bodies (PGBs) in the hippocampus, cerebellum, and piriform cortex than age-matched wild-type brains (J:216806)

• age-related PGBs resemble corpora amylacea (polysaccharide-based aggregates observed in aged human brain) and are also positive for other glycogen-binding proteins, such as laforin and BGP (the glycogen-degrading enzyme), stress-response proteins (such as ubiquitin, HSP70, and advanced glycation end products), parvalbumin and alpha-synuclein (J:216806)

• at 16 months of age, PGB distribution among astrocytes and neuronal cells is similar to than in aged wild-type brains (J:216806)

• 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 (J:218959)

increased brain glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in brain

• brain glycogen levels in the insoluble pellet is increased compared to in wild-type mice

abnormal glial cell morphology ( J:218959 )

• Laforin bodies accumulate in glial cells by 11 months of age

abnormal astrocyte morphology ( J:218959 )

• astrocytes often show Laforin bodies in their cytoplasm by 4 months of age

gliosis ( J:218959 )

• 11 month old mice show an increase in GFAP+ cells in the hippocampus, indicating gliosis

abnormal neuron morphology ( J:218959 )

• Laforin bodies accumulate in neurons by 11 months of age, in the neuronal somata of hippocampal PV+ interneurons and occasionally in their dendritic processes

hippocampal neuron degeneration ( J:218959 )

• degeneration of PV+ interneurons in the hippocampus, with mice showing a reduction in the number of PV+ neurons at 11 months of age

Lafora bodies ( J:165994 , J:218959 )

• mice exhibit increased Lafora bodies in the heart muscle, skeletal muscle, and brain compared with 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 (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)

abnormal excitatory postsynaptic potential ( J:218959 )

• 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

enhanced long-term potentiation ( J:218959 )

• mice show larger and longer-lasting LTPs

cardiovascular system

increased cardiac muscle glycogen level ( J:165994 )

• mice exhibit increased total glycogen levels in the heart muscle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lafora disease		DOID:3534	OMIM:254780	J:165994 , J:218959