Phenotypes associated with this allele

• Allele Symbol: Cacna1a^tm2.1Maag
• Allele Name: targeted mutation 2.1, Arn van den Maagdenberg
• Allele ID: MGI:3696966
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1a^tm2.1Maag/Cacna1a^tm2.1Maag	involves: 129P2/OlaHsd	MGI:3697451
cn2	Cacna1a^tg/Cacna1a^tm2.1Maag	involves: 129P2/OlaHsd * C57BL/6J * DBA/2J * FVB/N	MGI:5792057
cn3	Cacna1a^tm2.1Maag/Cacna1a^tm2.1Maag Tg(Pcp2-cre)2Mpin/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5903412
cn4	Cacna1a^tm1.1Ehess/Cacna1a^tm2.1Maag Tg(Pcp2-cre)2Mpin/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5707185
cn5	Cacna1a^tg/Cacna1a^tm2.1Maag Tg(Pcp2-cre)2Mpin/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2J * FVB/N	MGI:5792055
cn6	Cacna1a^tm1.1Ehess/Cacna1a^tm2.1Maag Tg(Atoh1-cre/Esr1*)14Fsh/0	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5707186
cn7	Cacna1a^tm2.1Maag/Cacna1a^tm2.2Maag Tg(EIIa-cre)C5379Lmgd/0	involves: 129P2/OlaHsd * FVB/N	MGI:3697450

Genotype
MGI:3697451

hm1

• Allelic Composition: Cacna1a^tm2.1Maag/Cacna1a^tm2.1Maag
• Genetic Background: involves: 129P2/OlaHsd

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

normal phenotype

no abnormal phenotype detected ( J:117062 )

• viable and fertile with no overt abnormalities

Genotype
MGI:5792057

cn2

• Allelic Composition: Cacna1a^tg/Cacna1a^tm2.1Maag
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * DBA/2J * FVB/N

behavior/neurological

dystonia ( J:233263 )

• mice injected with a lentivirus expressing cre recombinase into the midline or lateral cerebellum (to affect only 10-15% of the cerebellum) exhibit abnormal dystonic movements, with most isolated to a single body part, such as the hindlimb

• 90% of abnormal movements are tonic flexion or extension of the hindlimb, 8% are clonic movements of the head/neck and 2% are tonic flexion or extension of the trunk

muscle

dystonia ( J:233263 )

• mice injected with a lentivirus expressing cre recombinase into the midline or lateral cerebellum (to affect only 10-15% of the cerebellum) exhibit abnormal dystonic movements, with most isolated to a single body part, such as the hindlimb

• 90% of abnormal movements are tonic flexion or extension of the hindlimb, 8% are clonic movements of the head/neck and 2% are tonic flexion or extension of the trunk

abnormal muscle electrophysiology ( J:233263 )

• mice injected with a lentivirus expressing cre recombinase into the cerebellum exhibit an increase in electromyography amplitude of tibialis and gastrocnemius muscles

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
generalized dystonia		DOID:0050835		J:233263

Genotype
MGI:5903412

cn3

• Allelic Composition: Cacna1a^tm2.1Maag/Cacna1a^tm2.1Maag; Tg(Pcp2-cre)2Mpin/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

behavior/neurological

impaired righting response ( J:234599 )

• mice start showing problems righting themselves around P10-P12

tremors ( J:234599 )

• slight, but significant, increase in tremor with age

ataxia ( J:234599 )

• ataxia starts at P10-12

impaired balance ( J:234599 )

• mice start showing loss of balance during walking around P10-12

impaired coordination ( J:234599 )

• P18 mice perform worse on the rotarod than wild-type mice

• P30 mice are severely impaired on the rotarod, staying a shorter amount of time on the accelerating rod than wild-type mice, falling off the rod at a lower rotating speed, and do not improve over time

nervous system

abnormal brain interneuron morphology ( J:234599 )

• degeneration of molecular layer interneurons by P200-250

abnormal cerebellum morphology ( J:234599 )

• volume reductions and increase in surface density in all cerebellar nuclei

Purkinje cell degeneration ( J:234599 )

• neurodegenerative changes are first seen around P45, with argyrophylic staining in the Purkinje cell layer

• Purkinje cell degeneration in the cerebellum is clearly seen from P60, showing somatic sprouting and axonal swellings and progresses until P200-P250 when a significant decrease in Purkinje cell number is seen

abnormal cerebellar granule cell morphology ( J:234599 )

• degeneration of granule cells by P200-250

abnormal cerebellar molecular layer ( J:234599 )

• neurodegenerative changes are first seen around P45, with argyrophylic staining in the molecular layer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebellar ataxia		DOID:0050753		J:234599

Genotype
MGI:5707185

cn4

• Allelic Composition: Cacna1a^tm1.1Ehess/Cacna1a^tm2.1Maag; Tg(Pcp2-cre)2Mpin/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:217557 )

N • mice do not exhibit motor dysfunction on the rotarod

Genotype
MGI:5792055

cn5

• Allelic Composition: Cacna1a^tg/Cacna1a^tm2.1Maag; Tg(Pcp2-cre)2Mpin/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2J * FVB/N

behavior/neurological

dystonia ( J:233263 )

• mice exhibit dystonia that is more severe than in single Cacna1a^tg homozygotes

• more than 95% of abnormal movements are either tonic or clonic

• mice show a small (5%) but significant shift towards increased head/neck postures than in single Cacna1a^tg homozygotes

muscle

dystonia ( J:233263 )

• mice exhibit dystonia that is more severe than in single Cacna1a^tg homozygotes

• more than 95% of abnormal movements are either tonic or clonic

• mice show a small (5%) but significant shift towards increased head/neck postures than in single Cacna1a^tg homozygotes

Genotype
MGI:5707186

cn6

• Allelic Composition: Cacna1a^tm1.1Ehess/Cacna1a^tm2.1Maag; Tg(Atoh1-cre/Esr1*)14Fsh/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

behavior/neurological

behavior/neurological phenotype ( J:217557 )

N • mice do not exhibit motor dysfunction on the rotarod

Genotype
MGI:3697450

cn7

• Allelic Composition: Cacna1a^tm2.1Maag/Cacna1a^tm2.2Maag; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

lethality at weaning, complete penetrance ( J:117062 )

• die around P20-22 if left unaided

behavior/neurological

dystonia ( J:117062 )

• progressive, severe dystonia starting around P10-12

ataxia ( J:117062 )

• progressive, severe ataxia starting around P10-12

nervous system

abnormal synaptic acetylcholine release ( J:117062 )

• acetylcholine release is insensitive to 200 nM omega-Agatoxin-IVA in neuromuscular junctions

decreased neurotransmitter release ( J:117062 )

• about a 40% reduction in quantal content in neuromuscular junctions

growth/size/body

decreased body size ( J:117062 )

• at P20

muscle

dystonia ( J:117062 )

• progressive, severe dystonia starting around P10-12