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An early-onset congenic strain of the motor neuron degeneration (mnd) mouse
A Messer1, K Manley, J A Plummer
1Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
Abstract:
The mouse mutant motor neuron degeneration (mnd/mnd) has been proposed as a model of neuronal ceroid lipofuscinosis (NCL) on the basis of widespread abnormal accumulating lipopigment and neuronal and retinal degeneration. Clinically, the mutant on a C57Bl/6 genetic background shows a progressive motor abnormality starting by 6 months of age, with death prior to 12 months. When mnd is outcrossed to the AKR/J genetic background, ca. 40% of the mnd/mnd F2 progeny show early onset (onset by 4.5-5 months and death by 7 months). A congenic strain of mnd has now been produced by eight generations of backcross onto the AKR background. Mice on this background show average onset at 4 months, and most are moribund prior to 5.5 months. The early onset appears to correlate with levels of abnormal accumulating material, and should prove useful in elucidating NCL neurodegenerative mechanisms.
Insights
The mouse mutant motor neuron degeneration (mnd/mnd) model shows accelerated disease progression on an AKR/J genetic background. This early-onset model aids in understanding neuronal ceroid lipofuscinosis (NCL) neurodegeneration.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- The mouse mutant motor neuron degeneration (mnd/mnd) is a model for neuronal ceroid lipofuscinosis (NCL).
- It exhibits lipopigment accumulation and neurodegeneration.
- Wild-type C57Bl/6 background shows motor deficits starting at 6 months.
Purpose of the Study:
- To investigate the effect of the AKR/J genetic background on mnd/mnd phenotype.
- To develop an accelerated model for NCL research.
Main Methods:
- Outcrossing mnd/mnd mice to AKR/J.
- Creating a congenic strain through eight generations of backcrossing.
- Phenotypic analysis of motor abnormalities and survival rates.
Main Results:
- Crossing mnd/mnd to AKR/J resulted in early-onset disease in 40% of F2 progeny.
- Congenic mnd/mnd mice on AKR background showed onset at 4 months and death by 5.5 months.
- Early onset correlated with increased abnormal accumulating material.
Conclusions:
- The AKR/J background significantly accelerates the mnd/mnd phenotype.
- This congenic strain provides a valuable tool for studying NCL mechanisms.
- Further research can elucidate NCL neurodegenerative pathways using this model.