This recessive mutant is a hypomorph, caused by a spontaneous IAP insertion in intron 1, that provides a model for infantile neuroaxonal dystrophy (INAD). Mice homozygous for the Pla2g6m1J mutation can often be distinguished by a slight tremor at approximately 90 days of age. A gradual weight loss also begins at that time and progresses until premature death. Loss of grip strength presents between 60 to 80 days of age and progresses such that by 100 days of age homozygotes can no longer hang suspended in the wire-hang test for more than a few seconds. The average age of death is approximately 120 days and few homozygotes survive beyond 6 months of age. Astrocytes taken from 6 to 8 week old homozygotes and cultured for 14 to 16 days have aberrant ATP-stimulated calcium signaling. Capacitative calcium entry in these astroctyes was found to be only 45% that of wildtype controls. Tubulovesicular accumulations, called spheroids, are found throughout the neuropil of brains from late-stage homozygotes.
The Pla2g6m1J mutation arose spontaneously at The Jackson Laboratory in the C3H/HeJ inbred colony in 2000. This mutation has remained on a pure C3H/HeJ background, was backcrossed once to C3H/HeJ in approximately 2001, three generations after it was identified, and has been maintained since then primarily by sibling breeding with some cousin or closed colony breeding. Initially maintained by the Mouse Mutant Resource, this coisogenic mutant subline was transferred to the laboratory of Dr. Greg Cox in 2003.
|Allele Name||mutation 1, Jackson|
|Gene Symbol and Name||Pla2g6, phospholipase A2, group VI|
|Strain of Origin||C3H/HeJ|
|Molecular Note||A viral insertion occurred spontaneously in intron 1 upstream of the start codon, resulting in a dramatic reduction of transcript levels.|