Phenotypes associated with this allele

• Allele Symbol: Cacna2d2^du
• Allele Name: ducky
• Allele ID: MGI:1856022
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna2d2^du/Cacna2d2^du	involves: C3H * DBA/2J	MGI:3710678
hm2	Cacna2d2^du/Cacna2d2^du	involves: DBA/2J	MGI:4358494
hm3	Cacna2d2^du/Cacna2d2^du	TKDU	MGI:4358556
hm4	Cacna2d2^du/Cacna2d2^du	TKDU/DnJ	MGI:4358337

Genotype
MGI:3710678

hm1

• Allelic Composition: Cacna2d2^du/Cacna2d2^du
• Genetic Background: involves: C3H * DBA/2J

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

growth/size/body

decreased body weight ( J:121463 )

• body weight is severely reduced (19.1 grams) compared to wild-type (9.4 grams)

nervous system

abnormal motor neuron morphology ( J:121463 )

• fiber diameter at diaphragm NMJs is reduced by ~45% compared with wild-type

abnormal neuromuscular synapse morphology ( J:121463 )

• neuromuscular junction area (area staining for acetylcholine receptors) in ~40% smaller relative to wild-type mice (227 um² vs 374 um²)

abnormal miniature endplate potential ( J:121463 )

• MEPP amplitude in increased by ~40% at neuromuscular junctions (NMJs) compared to wild-type

decreased neurotransmitter release ( J:121463 )

• number of quanta released per supramaximal stimulus is reduced by ~25% compared to wild-type muscles

Genotype
MGI:4358494

hm2

• Allelic Composition: Cacna2d2^du/Cacna2d2^du
• Genetic Background: involves: DBA/2J

mortality/aging

decreased survivor rate ( J:116 )

• viability is reduced compared with normal littermates

behavior/neurological

abnormal gait ( J:116 )

• 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

reduced female fertility ( J:116 )

♀ • females rarely breed

reduced male fertility ( J:116 )

♂ • majority of homozygous males are poor breeders

growth/size/body

decreased body size ( J:116 )

• slightly smaller than normal littermates

Genotype
MGI:4358556

hm3

• Allelic Composition: Cacna2d2^du/Cacna2d2^du
• Genetic Background: TKDU

mortality/aging

premature death ( J:152373 )

• homozyogtes usually die between 35 and 40 days of age but a few survive for several months

behavior/neurological

ataxia ( J:152373 )

• the waddling and reeling gait lacks coordination

abnormal stationary movement ( J:152373 )

• 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

abnormal gait ( J:152373 )

• 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

induced hyperactivity ( J:152373 )

• extremely excitable

hindlimb paralysis ( J:152373 )

• periodic paraplegia with age

seizures ( J:152373 )

nervous system

seizures ( J:152373 )

abnormal hindbrain development ( J:152373 )

abnormal hindbrain morphology ( J:152373 )

• 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

abnormal medulla oblongata morphology ( J:152373 )

• the medulla oblongata is shorter than normal

decreased pons size ( J:152373 )

• the pons is shorter than normal and has less grey and ventral white matter

small cerebellum ( J:152373 )

• the cerebellum is smaller than normal although the forebrain is of normal size

abnormal CNS glial cell morphology ( J:152373 )

• although neuroglia appear morphologically normal, they are smaller than normal and there are fewer of them

abnormal neuron morphology ( J:152373 )

• 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

abnormal Purkinje cell morphology ( J:152373 )

• loss of Purkinje cells occurs

Purkinje cell degeneration ( J:152373 )

decreased Purkinje cell number ( J:152373 )

decreased neuron number ( J:152373 )

abnormal spinal nerve morphology ( J:152373 )

• the dorsal and ventral roots, spinal ganglia and nerves are severely reduced and smaller than normal

abnormal dorsal spinal root morphology ( J:152373 )

abnormal ventral spinal root morphology ( J:152373 )

abnormal spinal cord morphology ( J:152373 )

• 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

decreased spinal cord size ( J:152373 )

axonal dystrophy ( J:152373 )

• 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

abnormal glial cell physiology ( J:152373 )

• glial cell proliferation is found

abnormal myelination ( J:152373 )

• myelin deficiency is severe in the lateral lemniscus and ventral spinocerebellar tract and is detected at 16 days of age

growth/size/body

decreased body size ( J:152373 )

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

muscle

skeletal muscle hypoplasia ( J:152373 )

• the skeletal musculature is much reduced compared with controls

skeleton

abnormal vertebral column morphology ( J:152373 )

• 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

short vertebral body ( J:152373 )

Genotype
MGI:4358337

hm4

• Allelic Composition: Cacna2d2^du/Cacna2d2^du
• Genetic Background: TKDU/DnJ

behavior/neurological

induced hyperactivity ( J:5263 )

• homozygotes are hyperexcitable by 10 days of age

seizures ( J:5263 )

• appear at approximately 10 days of age

growth/size/body

postnatal growth retardation ( J:5263 )

• evident by 10 days of age

nervous system

nervous system phenotype ( J:43719 , J:70845 )

N • myelin formation, as assessed by semithin sections and electron microscopy, is normal in the optic nerve, corpus callosum, and spinal cord (J:43719)

N • at 21 days of age there is no loss of cell bodies in the Purkinje cell layer or granule layer (J:70845)

seizures ( J:5263 )

• appear at approximately 10 days of age

decreased brain weight ( J:5263 )

• the brain down through the foramen magnum weighs less than normal, primarily because of the lower weight of the hindbrain and spinal cord portion

abnormal spinal cord white matter morphology ( J:43719 )

• spinal cord white matter has fewer small diameter axons

abnormal myelination ( J:5263 )

• 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

endocrine/exocrine gland phenotype ( J:5263 )

N • protein bound iodine levels in serum are normal indicating normal thyroid function

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:5175 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic generalized epilepsy		DOID:1827	OMIM:600669	J:70845