Phenotypes Associated with This Genotype

Genotype
MGI:4415286

• Allelic Composition: Pla2g6^m1Sein/Pla2g6^m1Sein
• Genetic Background: C57BL/6JJcl-Pla2g6^m1Sein

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

mortality/aging

premature death ( J:153195 , J:155328 )

• homozygotes die by 4 months of age (J:153195)

• mice die before 18 weeks of age (J:155328)

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:155328 )

• at 7 to 8 weeks, all mice exhibit abnormal movement unlike wild-type mice

• motor impairments worsen with age

abnormal motor coordination/balance ( J:153195 )

• homozygotes have a progressive impairment of motor function

ataxia ( J:155328 )

• severe prior to 10 weeks of age

decreased grip strength ( J:155328 )

• at 7 weeks, mice exhibit impaired performance in a hanging grip test compared with wild-type mice

• after 10 weeks, mice cannot hold their body on an inverted plate unlike wild-type mice

hindlimb paralysis ( J:155328 )

• at 12 weeks, mice drag their hindlimbs unlike wild-type mice

nervous system

abnormal nervous system morphology ( J:153195 , J:155328 )

• homozygotes show accumulation of spheroids, axonal swelling, and ubiquitin-positive granular deposits in brain stem gracile nuclei, cerebellar white mater, spinal cord and peripheral nerves (J:153195)

• at 16 weeks, mice exhibit spheroids in gracile and cuneate nuclei of the brainstem, cerebral cortex, thalamus, substantia nigra, trigeminal motor nucleus, cerebellar dentate nucleus, lumbar spinal anterior horn, lumbar corticospinal tract, and lumbar posterior funiculus unlike in wild-type mice (J:155328)

abnormal brain morphology ( J:153195 )

abnormal brain white matter morphology ( J:153195 )

abnormal brainstem morphology ( J:153195 )

abnormal axon morphology ( J:153195 )

abnormal spinal cord morphology ( J:153195 )

neurodegeneration ( J:183152 )

axonal dystrophy ( J:183152 )

abnormal astrocyte physiology ( J:183152 )

• astrocytes taken from 6 to 8 week old homozygotes and cultured for 14 to 16 days have diminished ATP-stimulated calcium signalling with capacitative calcium entry in these astrocytes reduced by 43% compared with controls

muscle

muscular atrophy ( J:153195 )

skeletal muscle atrophy ( J:155328 )

• in the hindlimb

immune system

decreased double-positive T cell number ( J:155328 )

growth/size/body

weight loss ( J:155328 )

• mice become emaciated as they age

hematopoietic system

decreased double-positive T cell number ( J:155328 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodegeneration with brain iron accumulation 2a		DOID:0110735	OMIM:256600	J:155328