Phenotypes associated with this allele

• Allele Symbol: Cacnb4^lh
• Allele Name: lethargic
• Allele ID: MGI:1856936
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacnb4^lh/Cacnb4^lh	B6EiC3Sn a/A-Cacnb4^lh/J	MGI:3797410
hm2	Cacnb4^lh/Cacnb4^lh	BALB/cGn-Cacnb4^lh	MGI:3797420
hm3	Cacnb4^lh/Cacnb4^lh	involves: BALB/cGn	MGI:3797485
hm4	Cacnb4^lh/Cacnb4^lh	involves: BALB/cGn * C3H/HeSnJ * C57BL/6JEi	MGI:3700747

Genotype
MGI:3797410

hm1

• Allelic Composition: Cacnb4^lh/Cacnb4^lh
• Genetic Background: B6EiC3Sn a/A-Cacnb4^lh/J

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

immune system

absent thymus corticomedullary boundary ( J:5281 )

• the boundary between the cortex and medulla is not visible as in wild-type mice

small thymus ( J:5281 )

• between 26 and 40 days of age

abnormal thymus involution ( J:5281 )

• mice undergo thymus involution

decreased lymphocyte cell number ( J:5281 )

• in the thymus and spleen

decreased double-positive T cell number ( J:115345 )

• in mice older than 2 weeks of age when the onset of neuropathy occurs

• however, prior to 2 weeks of age mice exhibit normal T cell development

small spleen ( J:5281 )

• between 15 days and 10 months of age

abnormal CD4-positive, alpha-beta T cell physiology ( J:115345 )

• initial peak and plateau calcium responses are attenuated compared to in wild-type mice

abnormal Peyer's patch germinal center morphology ( J:5281 )

• absent

decreased Peyer's patch number ( J:5281 )

small Peyer's patches ( J:5281 )

abnormal lymph node morphology ( J:5281 )

• between 18 and 35 days of age, mice exhibit fewer lymphatic follicles compared to wild-type mice

enlarged lymph nodes ( J:5281 )

• mice older than 5 months exhibit enlarged lymph nodes compared to wild-type mice

decreased interferon-gamma secretion ( J:115345 )

abnormal interleukin secretion ( J:115345 )

• IL-4 production is reduced

decreased interleukin-2 secretion ( J:115345 )

• TCR-mediated IL-2 production is partially inhibited

growth/size/body

cachexia ( J:5281 )

• between 26 and 40 days of age

digestive/alimentary system

diarrhea ( J:5281 )

• between 26 and 40 days of age

vision/eye

vision/eye phenotype ( J:80080 )

N • both a- and b-waves appear normal in mutant mice

N • histological analysis indicates that retinal morphology is normal

abnormal eye electrophysiology ( J:136113 )

• electroretinograms generated by retinal pigment epithelial cells are reduced compared to in wild-type mice

• maximum amplitude of the light peak is reduced and overall sensitivity is decreased compared to in wild-type mice

hematopoietic system

absent thymus corticomedullary boundary ( J:5281 )

• the boundary between the cortex and medulla is not visible as in wild-type mice

small thymus ( J:5281 )

• between 26 and 40 days of age

abnormal thymus involution ( J:5281 )

• mice undergo thymus involution

decreased lymphocyte cell number ( J:5281 )

• in the thymus and spleen

decreased double-positive T cell number ( J:115345 )

• in mice older than 2 weeks of age when the onset of neuropathy occurs

• however, prior to 2 weeks of age mice exhibit normal T cell development

small spleen ( J:5281 )

• between 15 days and 10 months of age

abnormal CD4-positive, alpha-beta T cell physiology ( J:115345 )

• initial peak and plateau calcium responses are attenuated compared to in wild-type mice

endocrine/exocrine glands

absent thymus corticomedullary boundary ( J:5281 )

• the boundary between the cortex and medulla is not visible as in wild-type mice

small thymus ( J:5281 )

• between 26 and 40 days of age

abnormal thymus involution ( J:5281 )

• mice undergo thymus involution

Genotype
MGI:3797420

hm2

• Allelic Composition: Cacnb4^lh/Cacnb4^lh
• Genetic Background: BALB/cGn-Cacnb4^lh

mortality/aging

premature death ( J:12166 )

• mice exhibit high mortality rates between 3 and 4 weeks of age

reproductive system

absent corpus luteum ( J:12166 )

♀

reduced fertility ( J:12166 )

• mice exhibit reduced reproductivity

immune system

abnormal thymus involution ( J:12166 )

• mice undergo thymus involution soon after the onset of neurological symptoms

increased length of allograft survival ( J:5766 )

• between 15 to 30 days of age, mice fail to reject skin grafts as wild-type mice do

• however, by 45 days of age graft rejection is normal

nervous system

pituitary gland hyperplasia ( J:12166 )

• pituitary glands exhibit an increase in cellular population density compared to in wild-type pituitaries

behavior/neurological

abnormal behavior ( J:28465 )

• mice sit up with front feet contracted for several minutes

abnormal fear/anxiety-related behavior ( J:28465 )

• mice appear nervous

abnormal locomotor activation ( J:28465 )

• mice exhibit difficulty in moving forward and make long pauses between movements, often hunch the back and raise first the front foot then the hind foot

endocrine/exocrine glands

pituitary gland hyperplasia ( J:12166 )

• pituitary glands exhibit an increase in cellular population density compared to in wild-type pituitaries

absent corpus luteum ( J:12166 )

♀

abnormal thymus involution ( J:12166 )

• mice undergo thymus involution soon after the onset of neurological symptoms

growth/size/body

postnatal growth retardation ( J:12166 )

hematopoietic system

abnormal thymus involution ( J:12166 )

• mice undergo thymus involution soon after the onset of neurological symptoms

Genotype
MGI:3797485

hm3

• Allelic Composition: Cacnb4^lh/Cacnb4^lh
• Genetic Background: involves: BALB/cGn

behavior/neurological

lethargy ( J:28466 )

• when removed from a swim test mice exhibit slowed responses with hindlimbs appearing weak and he animal unable to ascend a 45 degree incline for 10 to 15 minutes

abnormal gait ( J:28466 )

• at 14 to 16 days of age, mice exhibit a mild gait instability

convulsive seizures ( J:28466 )

• mice exhibit clonic and/or tonic seizures

• excitement during seizure worsens the severity of the seizure

• however, gentle handling quells the seizures until released

• sometimes mice exhibit a Jacksonian march during seizures

nervous system

convulsive seizures ( J:28466 )

• mice exhibit clonic and/or tonic seizures

• excitement during seizure worsens the severity of the seizure

• however, gentle handling quells the seizures until released

• sometimes mice exhibit a Jacksonian march during seizures

abnormal nerve conduction ( J:6556 )

• mice exhibit adult motor nerve conduction velocities at 3 months of again instead of 5 as in wild-type mice

decreased nerve conduction velocity ( J:6556 )

• peripheral motor nerves exhibit reduced conduction velocity and prolonged distal latency

immune system

increased IgG1 level ( J:5883 )

hematopoietic system

increased IgG1 level ( J:5883 )

Genotype
MGI:3700747

hm4

• Allelic Composition: Cacnb4^lh/Cacnb4^lh
• Genetic Background: involves: BALB/cGn * C3H/HeSnJ * C57BL/6JEi

nervous system

nervous system phenotype ( J:121463 )

N • synaptic electrophysiology including neurotransmitter release and end plate potentials, as well as responses to channel inhibitors is not different from wild-type NMJs

seizures ( J:1484 )

• mice exhibit absence seizures

• seizures are increased by treatment with GAB agonists and decreased by treatment with GABA antagonists

clonic seizures ( J:79139 )

• mice have attacks with clonic movements of the limbs most apparent at 4 weeks of age

tonic seizures ( J:79139 )

• mice show periods of tonic extension or retraction of the limbs at 4 weeks of age

abnormal motor neuron morphology ( J:121463 )

• synaptic electrophysiology including neurotransmitter release and end plate potentials, as well as responses to channel inhibitors is not different from wild-type NMJs

abnormal neuromuscular synapse morphology ( J:121463 )

• neuromuscular junction area (area staining for acetylcholine receptors) in ~38% smaller relative to wild-type mice (277 um² vs 446 um²)

abnormal brain wave pattern ( J:1484 , J:79139 )

• mice exhibit bilaterally synchronous electrographic bursts (seizures) that last 1.5 s with a frequency of 127 per hour (J:1484)

• EEG of saline-treated mice display frequent polyspike discharges (J:79139)

abnormal CNS synaptic transmission ( J:106959 )

• peak current densities of low voltage-activated (LVA) calcium channels in thalamocortical neurons at membrane potential of -50 mV are increased by 51% compared to control

• peak current densities of high voltage calcium channels (HVA) in TC neurons are similar to wild-type

behavior/neurological

impaired behavioral response to xenobiotic ( J:1484 )

• phenytoin and carbamazepine fail to reduce seizure frequency

abnormal motor capabilities/coordination/movement ( J:79139 )

• transient periods of severe motor disability are superimposed on the more minor abnormalities

impaired righting response ( J:79139 )

• mice tend to fall and are unable to regain upright position, becoming less frequent by 5-6 weeks of age

ataxia ( J:79139 )

• mice show wide stance, imprecise limb placement, poor timing and interlimb coordination, and a staggering gait, all characteristic of ataxia

impaired coordination ( J:79139 )

• mice perform very poorly in rotarod tests, falling off the rod whereas wild-type remain on for ~length of test

abnormal posture ( J:79139 )

• mice show periods of abnormal flexion or extension of the trunk most apparent at 4 weeks of age

decreased locomotor activity ( J:79139 )

• mice show transient periods of reduced locomotor activity when tested in photocell chambers

circling ( J:79139 )

• mice display circling, becoming less frequent by 5-6 weeks of age

seizures ( J:1484 )

• mice exhibit absence seizures

• seizures are increased by treatment with GAB agonists and decreased by treatment with GABA antagonists

clonic seizures ( J:79139 )

• mice have attacks with clonic movements of the limbs most apparent at 4 weeks of age

tonic seizures ( J:79139 )

• mice show periods of tonic extension or retraction of the limbs at 4 weeks of age

muscle

facial muscle spasm ( J:79139 )

• mice display facial twitching, becoming less prominent by 5-6 weeks of age