Phenotypes Associated with This Genotype

Genotype
MGI:4418721

• Allelic Composition: nad/nad
• Genetic Background: C(D2)-nad

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

mortality/aging

premature death ( J:156089 )

• homozygotes usually die by 6 months of age

nervous system

axonal dystrophy ( J:156089 )

• spheroids are found in the grey and white matter of the midbrain, brain stem, and all levels of the spinal cord, with the highest density being found in the medulla, predominantly in the sensory nuclei, and in the dorsal horns and dorsal funiculi of the spinal cord, but speroids are absent from peripheral nerves, distal axon terminals of the skin, optic nerve, retina, dorsal root ganglia, trigeminal ganglia, or cerebral hemispheres rostral to the anterior commissure

• transmission electron microscopy of the nuclei gracilis and cuneatus from the medulla and dorsal funiculi from the cervical spinal cord shows that the spheroids consist of swollen axons, many of which are ruptured, and two morphological types of accumulation were found, with the most prevalent being composed of stacks of membranes, tubulovesicular profiles, and synaptic vesicles, and the more rare type being composed of accumulatioins of degenerate mitochondria, myelin figures, neurofilaments, and membranous dense bodies

behavior/neurological

limb grasping ( J:156089 )

• by 3 to 4 weeks of age when lifted by the tail homozygotes adduct their hind legs and clasp their hind paws together

ataxia ( J:156089 )

• hindlimb spasticity and ataxia are found as early as 3 weeks of age

abnormal posture ( J:156089 )

• by 4 weeks of age homozygotes display a hunched posture, crouched stance, stilted gait, and atrophy of the lumbar and hindlimb musculature

hunched posture ( J:156089 )

abnormal gait ( J:156089 )

• stilted gait by 4 weeks of age

paraparesis ( J:156089 )

reproductive system

abnormal spermatogenesis ( J:156089 )

♂ • a mild defect in spermatogenesis is found in adults

male infertility ( J:156089 )

♂ • males are unable to breed, likely as a result of hindlimb weakness or paraparesis

growth/size/body

decreased body weight ( J:156089 )

• prior to 3 weeks of age homozygotes are smaller than control littermates and by 4 weeks of age is 10% to 30% lighter than control littermates

muscle

skeletal muscle atrophy ( J:156089 )

• by 4 weeks of age atrophy of the lumbar and hindlimb musculature are found

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:156089 )

N • complete blood count and clinical biochemistry values show no significant abnormalities

immune system

abnormal bronchus-associated lymphoid tissue morphology ( J:156089 )

• discrete nodular accumulations of lymphocytes and plasma cells are found in the lungs of approximately 95% of homozgyotes, with the hyperblastic lymphoid nodules more frequently found in sub-pleural sites distant from conducting airways

integument

disheveled coat ( J:156089 )

• by 4 weeks of age homozygotes have an unthrifty pelage

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neurodegeneration with brain iron accumulation 2a		DOID:0110735	OMIM:256600	J:156089