Mouse Genome Informatics
hm1
    Cacna2d2du/Cacna2d2du
involves: C3H
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• body weight is severely reduced (19.1 grams) compared to wild-type (9.4 grams)

nervous system
• fiber diameter at diaphragm NMJs is reduced by ~45% compared with wild-type
• neuromuscular junction area (area staining for acetylcholine receptors) in ~40% smaller relative to wild-type mice (227 um2 vs 374 um2)
• MEPP amplitude in increased by ~40% at neuromuscular junctions (NMJs) compared to wild-type
• number of quanta released per supramaximal stimulus is reduced by ~25% compared to wild-type muscles


Mouse Genome Informatics
hm2
    Cacna2d2du/Cacna2d2du
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• viability is reduced compared with normal littermates

behavior/neurological
• waddling gait appears after 14 days of age, is seldom apparent before 19 days of age, involves a hunched appearance and a toeing out of the hind feet, and as they age they develop a reeling gait with a tendency to fall to one side

reproductive system
• females rarely breed (J:116)
• majority of homozygous males are poor breeders (J:116)

growth/size/body
• slightly smaller than normal littermates


Mouse Genome Informatics
hm3
    Cacna2d2du/Cacna2d2du
TKDU
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• homozyogtes usually die between 35 and 40 days of age but a few survive for several months

behavior/neurological
• the waddling and reeling gait lacks coordination
• extremely excitable
• waddling gait with the toes of the hind feet turned out, and unable to run normally but instead hop with inwardly rotated ankles or hocks, and with age the gait deteriorates so that they reel with the hind limbs and tail extended and frequently fall on their sides and exhibit periodic paraplegia
• homozygotes assume a frog-like position with the hind legs abducted at the hips, flexed at the knees, and the metatarsus kept flat on the surface
• periodic paraplegia with age

nervous system
• all hindbrain structures are smaller than normal, with the cerebellum most severely affected, and both the white and grey matter of the medulla and cerebellum is reduced and the fiber tracts shortened
• the pontine neurons are smaller and less numerous than normal, the crossing fibers and nucleus of the trapezoid body are significantly reduced in size, the corticospinal tract and medial lemniscus are reduced in a sagittal plane
• the medulla oblongata is shorter than normal
• the pons is shorter than normal and has less grey and ventral white matter
• the cerebellum is smaller than normal although the forebrain is of normal size
• although neuroglia appear morphologically normal, they are smaller than normal and there are fewer of them
• although normal in forebrain and midbrain, the neurons in the hindbrain and spinal cord are less numerous and smaller than normal, particularly in the trapezoid body, the pontine, olivary, and fastigial nuclei, and the spinal ganglia
• loss of Purkinje cells occurs
• the dorsal and ventral roots, spinal ganglia and nerves are severely reduced and smaller than normal
• the spinal cord is thinner and shorter than normal, deficient in white and grey matter, with the funicular and short fiber tracts of the white matter smaller than normal and neurons, glia, glial fibers, and spinal ganglia in the grey matter smaller than normal
• axonal dystrophy is consistently found in the spinocerebellar tract, lateral lemniscus, vestibulospinal and cerebellospinal tracts, in the medulla, in Purkinje cell axons as they traverse the granule cell layer, and in other fibers coursing adjacent to and between the neurons of the intracerebellar nuclei, with greatest severity in and around the fastigial nuclei
• axonal dystrophy is often severe in the dorsal and ventral root, cauda equina, and fibers of peripheral nerves
• characterized by coarse or bulbous bead-like thickenings and first detected at 16 days of age
• glial cell proliferation is found
• myelin deficiency is severe in the lateral lemniscus and ventral spinocerebellar tract and is detected at 16 days of age

growth/size/body
• homozygotes are only half to three quarters of the size of normal controls

muscle
• the skeletal musculature is much reduced compared with controls

skeleton
• the vertebral column and spinal cord are undersized and thin, and the smaller size and underdevelopment of the vertebral column progresses caudad
• the vertebral bodies and spinous processs are shorter than normal, and the bony spicules and trabeculae are thinner and more delicate


Mouse Genome Informatics
hm4
    Cacna2d2du/Cacna2d2du
TKDU/DnJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• homozygotes are hyperexcitable by 10 days of age
• appear at approximately 10 days of age

growth/size/body
• evident by 10 days of age

nervous system
N
• myelin formation, as assessed by semithin sections and electron microscopy, is normal in the optic nerve, corpus callosum, and spinal cord (J:43719)
• at 21 days of age there is no loss of cell bodies in the Purkinje cell layer or granule layer (J:70845)
• appear at approximately 10 days of age
• the brain down through the foramen magnum weighs less than normal, primarily because of the lower weight of the hindbrain and spinal cord portion
• spinal cord white matter has fewer small diameter axons
• there is a cerebroside deficiency in the central nervous system at 15 days of age and it is more pronounced in the hindbrain and spinal cord segment at all timepoints assessed from 18 to 57 days of age
• cerebroside synthesis is delayed in the hindbraind and spinal cord segment by at least 1 week to 10 days

endocrine/exocrine glands
N
• protein bound iodine levels in serum are normal indicating normal thyroid function (J:5263)

homeostasis/metabolism
• non-specific esterases of liver and kidney show developmental changes that differ from normal