All Phenotypes Cacna1a<tg-rol> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1a^tg-rol/Cacna1a^tg-rol	involves: C3Hf/Nga * C57BL/6 * SIII	MGI:4834663
hm2	Cacna1a^tg-rol/Cacna1a^tg-rol	involves: C57BL/6 * SIII	MGI:3624868
ht3	Cacna1a^tg-rol/Cacna1a⁺	involves: C3Hf/Nga * C57BL/6 * SIII	MGI:4834664
ht4	Cacna1a^tg-rol/Cacna1a^tg	involves: C3H * C57BL/6 * DBA/2J * SIII	MGI:4833694

Allelic Composition	Cacna1a^tg-rol/Cacna1a^tg-rol
Genetic Background	involves: C3Hf/Nga * C57BL/6 * SIII

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1a^tg-rol mutation (1 available); any Cacna1a mutation (115 available)

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

growth/size/body

decreased body weight ( J:3611 )

homeostasis/metabolism

increased noradrenaline level ( J:164122 )

• noradrenaline level is significantly elevated in the cerebellum

abnormal glucose homeostasis ( J:3611 )

• mice show marked increases in local cerebral glucose utilization in the structures of the basal ganglia such as globus pallidus, entopeduncular nucleus, substantia nigra pars compacta and pars reticulata, and subthalamic nucleus, and some increase in the limbic system and brainstem such as the CA1 and CA3 region of the hippocampus, lateral habenula, pedunculopontine nucleus, red nucleus, and ventral tegmental area, indicating a basal ganglia dysfunction

• no alternation in local cerebral glucose utilization in the cerebellum

nervous system

small cerebellum ( J:164122 )

• cerebellum wet weight is 76% of controls

abnormal nervous system physiology ( J:3611 )

• no alternation in local cerebral glucose utilization in the cerebellum

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

mortality/aging

mortality/aging ( J:15016 )

N	• Background Sensitivity: viability is background dependent

cellular

increased apoptosis ( J:107924 )

• greater numbers of TUNEL-positive cells are detected in the granule cell layer of mutant mice than are found in wild-type (22.1 cells/section in mutants vs 4.6 cells/section in wild-type) at 20 days of age; there is no difference in numbers of apoptotic cells seen at 10 or 15 days

behavior/neurological

ataxia ( J:12735 , J:109231 )

• homozygous mice are identifiable between 10 and 14 days of age by a creeping or rolling gait (J:12735)

• mice show ataxic behavior around P10 (J:109231)

impaired limb coordination ( J:12735 )

• at 10-14 days of age, poor motor control of the hindlimbs can be observed

weakness ( J:12735 )

• mutants born on an inbred background are weak, but when crossed to produce congenic or co-isogenic lines, mice are more viable

abnormal nursing ( J:12735 )

• females have a reduced ability to nurse pups

nervous system

abnormal brainstem morphology ( J:6553 )

• net weight of the brain stem is slightly reduced

abnormal cerebellum morphology ( J:12735 , J:107924 )

• in mutant mice, many apoptotic granule cells are seen in the cerebellum at 20 days of age (J:107924)

small cerebellum ( J:6553 )

• cerebellum weight is reduced to 75% of the controls

cerebellum atrophy ( J:107924 )

• regional atrophy is observed in the anterior lobe of the cerebellum in mutants

cerebellum hypoplasia ( J:15016 )

• size ratio of cerebellum to cerebrum in mutants is 0.35 in medial-dorsal aspect and 0.25 mid-sagitally compared to 0.40 and 0.30 respectively in wild-type, indicating cerebellar hypoplasia

abnormal CNS synaptic transmission ( J:109231 )

• application of AMPA to acutely dissociated Purkinje cells results in larger maximum inward current densities at lower AMPA concentrations than in wild-type or Cacna1^tg homozygotes

abnormal excitatory postsynaptic currents ( J:109231 )

• parallel fiber (PF) stimulation is less effective in eliciting EPSCs (PF-EPSC) in ataxic mutants than in wild-type at stimulation intensities of 3-15 Volts

prolonged excitatory postsynaptic current decay time ( J:164115 )

• decay time constant of climbing fiber-EPSCs (CF-EPSC) is significantly greater than in wild-type or Cacna1^tg homozygotes; rise times of CF-EPSCs of both mutant strains and wild-type are not significantly different

abnormal miniature excitatory postsynaptic currents ( J:109231 )

• miniature EPSCs have a larger decay time constant than wild-type or Cacna1^tg homozygotes

enhanced paired-pulse facilitation ( J:109231 )

• paired-pulse facilitation (PPF) magnitudes are significantly greater at 50 msec interpulse intervals than in wild-type Cacna1^tg homozygotes

reproductive system

reduced female fertility ( J:12735 )

• females are fertile but do not breed well

reduced male fertility ( J:12735 )

• males rarely breed

muscle

abnormal muscle electrophysiology ( J:164115 )

• muscles are very sensitive to low calcium, with contractions of flexor digitorium brevis muscles decreasing to about 40% in presence of 0.5 mM calcium

• flexor digitorium brevis muscles are more sensitive to low calcium than diaphragms

muscle weakness ( J:164115 )

• weakness of fast leg muscle

homeostasis/metabolism

decreased glutamic acid level ( J:6553 )

• concentration of glutamate is reduced to 86% of the control value in the cerebellum

increased glycine level ( J:6553 )

• concentration of glycine is increased in the cerebellum but not in other regions

increased taurine level ( J:6553 )

• concentration of taurine is increased in the cerebellum but not in other regions

abnormal metabolism ( J:15508 )

• thyrotropin releasing hormone (TRH) turnover is abnormally regulated in serotonergic neurons

• serotonin antagonists and serotonin receptor antagonists increase TRH content in the spinal cord instead of causing a decrease as in controls

decreased choline O-acetyltransferase activity ( J:6553 )

• choline acetyltransferase activity in the stratum and the frontal cortex is reduced

increased brain tyrosine 3-monooxygenase activity ( J:6553 )

• increase in activity of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis, in the cerebellum, spinal cord, medulla, oblongata, thalamus, and hypothalamus

abnormal response/metabolism to endogenous compounds ( J:15508 )

• serotonin does not increase thyrotropin releasing hormone (TRH) content in the spinal cord as it does in control mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lambert-Eaton myasthenic syndrome		DOID:0050214		J:164115

Allelic Composition	Cacna1a^tg-rol/Cacna1a⁺
Genetic Background	involves: C3Hf/Nga * C57BL/6 * SIII

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1a^tg-rol mutation (1 available); any Cacna1a mutation (115 available)

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:3611 )

• mice show an intermediate increase in local cerebral glucose utilization in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata, and subthalamic nucleus

nervous system

abnormal nervous system physiology ( J:3611 )

• mice show an intermediate increase in local cerebral glucose utilization in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata, and subthalamic nucleus

Allelic Composition	Cacna1a^tg-rol/Cacna1a^tg
Genetic Background	involves: C3H * C57BL/6 * DBA/2J * SIII

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1a^tg mutation (1 available); any Cacna1a mutation (115 available)
Cacna1a^tg-rol mutation (1 available); any Cacna1a mutation (115 available)

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

mortality/aging

mortality/aging ( J:14882 )

N	• normal life span

behavior/neurological

behavior/neurological phenotype ( J:14882 )

N	• mutants do not exhibit epileptiform seizures that are seen in single homozygous Cacna1a^tg mice

abnormal locomotor behavior ( J:14882 )

ataxia ( J:14882 )

abnormal gait ( J:14882 )

• develop wobbly gait that is similar to that of single homozygous Cacna1a^tg-rol but more severe than in single homozygous Cacna1a^tg mice

nervous system

abnormal nervous system morphology ( J:14882 )

• neuromuscular disorder appears at 2 weeks of age, at a similar time frame as in single homozygous Cacna1a^tg-rol mice

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