Phenotypes Associated with This Genotype

Genotype
MGI:5312936

• Allelic Composition: Nhlrc1^tm1.2Geno/Nhlrc1^tm1.2Geno
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

behavior/neurological

abnormal object recognition memory ( J:181559 )

• in an object recognition task, mice exhibit decreased episodic memory compared with wild-type mice

abnormal motor capabilities/coordination/movement ( J:181559 )

• mice exhibit impaired spontaneous motor activity and motor coordination compared with wild-type mice

limb grasping ( J:181559 )

myoclonus ( J:181559 )

• myoclonic jerk with or without electroencephalographic correlation

abnormal spike wave discharge ( J:181559 )

• mice exhibit spontaneous low frequency spike, spike-wave and poly spike-wave complexes with or without correlated myoclonic jerks compared with wild-type mice

• at 3 months, mice exhibit epileptiform activity unlike wild-type mice

• however, mice do not exhibit epileptiform activity or convulsive movement with intermittent light stimulation

nervous system

myoclonus ( J:181559 )

• myoclonic jerk with or without electroencephalographic correlation

abnormal spike wave discharge ( J:181559 )

• mice exhibit spontaneous low frequency spike, spike-wave and poly spike-wave complexes with or without correlated myoclonic jerks compared with wild-type mice

• at 3 months, mice exhibit epileptiform activity unlike wild-type mice

• however, mice do not exhibit epileptiform activity or convulsive movement with intermittent light stimulation

abnormal brain interneuron morphology ( J:181559 )

• at P16, interneurons accumulate intracellular Lafora bodies unlike wild-type mice

Lafora bodies ( J:181559 )

• at 3 months, mice exhibit accumulation of Lafora bodies in the brain interneurons (olfactory bulb, hippocampus, superior and inferior colliculi, preoptic area, lateral geniculate nucleus, cerebellum and pontine nuclei), heart, vascular smooth muscle and skeletal muscle with progressive increase as mice age unlike wild-type mice

• Lafora bodies accumulate in the neuroretina and cortex (enriched in the molecular and deep layers) unlike in wild-type mice

• glycolytic type II fibers in the rectus femoris accumulate Lafora bodies unlike in wild-type mice

• Lafora bodies are non-membrane bound in the sarcoplasm of myocytes in the myocardium and skeletal muscle

• Lafora bodies are larger than in Epm2a^tm1Kzy homozygotes

cellular

abnormal autophagy ( J:181559 )

• autophagy via an mTOR-independent mechanism (particularly degradation of long-lived proteins) is impaired in the brain and mouse embryonic fibroblasts

muscle

myoclonus ( J:181559 )

• myoclonic jerk with or without electroencephalographic correlation

pigmentation

lipofuscinosis ( J:181559 )

• lipofuscin granules are observed in the cytoplasm of neurons in the cortex

homeostasis/metabolism

abnormal autophagy ( J:181559 )

• autophagy via an mTOR-independent mechanism (particularly degradation of long-lived proteins) is impaired in the brain and mouse embryonic fibroblasts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lafora disease		DOID:3534	OMIM:254780	J:181559