Clcn1<adr-mto> Spontaneous Allele Detail MGI Mouse (MGI:1855953)

Clcn1^adr-mto
Spontaneous Allele Detail

Nomenclature

Symbol:	Clcn1^adr-mto
Name:	chloride channel 1; myotonia
MGI ID:	MGI:1855953
Synonyms:	adr^mto
Gene:	Clcn1 Location: Chr6:42236684-42264655 bp, + strand Genetic Position: Chr6, 22.5 cM

Mutation
origin

Strain of Origin:

SWR/J

Mutation
description

Allele Type:	Spontaneous
Mutation:	Single point mutation
	A nonsense mutation at codon 47 (C to T transition) is predicted to change an arginine residue into a stop codon ahead of the first transmembrane region of Clcn1. Northern analyses of adult skeletal muscle using a 5' and a 3' rat cDNA Clcn1 probe detected wild-type size transcript in homozygous mutant mice (J:752). (J:16954)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 1 strain available Cell Lines: 0 lines available
Carrying any Clcn1 Mutation:	10 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1
behavior/neurological		√
altered righting response		√
abnormal voluntary movement		√
impaired limb coordination		√
abnormal gait		√
		hm1
growth/size		√
decreased body weight		√
		hm1
muscle		√
muscle phenotype		N
increased skeletal muscle mass		√
abnormal muscle physiology		√
abnormal muscle electrophysiology		√
impaired muscle relaxation		√
		hm1
nervous system		√
axon degeneration		√
		hm1
reproductive system		√
reduced fertility		√
		hm1
skeleton		√
kyphosis		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

hm1

Clcn1^adr-mto/Clcn1^adr-mto

SWR/J

behavior/neurologicalaltered righting response (J:14251)

mice exhibit an arrested development of righting response

abnormal voluntary movement (J:14251, J:6814)

mice exhibit stiffening of hindlimbs when supine with difficulty righting and stiffening of hindlimbs after rapid movement (J:14251)

abnormal phenotype is visible at 2 weeks of age and is progressive (J:14251)

at 2 weeks of age, mice exhibit stiff extensor postures of the limbs when gently dropped from a height of about 10 cm (J:6814)

when tested after 2 hours at 5 degrees Celsius, extensor posture is elicited more easily and its duration is increased by 50% (J:6814)

unlike in wild-type mice, scratching motion with hindlimb is not rapid (J:6814)

when place in an ice water bath mice exhibit a stiff extensor posture of the hindlimbs that is most prominent in the first minute and gradually subsides (J:6814)

impaired limb coordination (J:6814)

mice are capable of swimming but alternate movements of the hindlimbs are not well coordinated

abnormal gait (J:6814)

mice exhibit a slightly stiff gait and walk slower than wild-type mice

musclemuscle phenotype (J:6814)

mice do not display muscle fiber necrosis, grouped atrophy or inflammatory infiltrates

increased skeletal muscle mass (J:6814)

by day 70, mice exhibit increased muscle bulk in the neck and shoulder girdle muscles compared to wild-type mice

abnormal muscle physiology (J:6814)

percussion of muscles occasionally produces a sustained local contraction with sustained posturing

however, muscle weakness is not observed

abnormal muscle electrophysiology (J:14251, J:6814)

mice exhibit myotonic discharges in limbs, abdominal, tongue, and eye muscles (J:14251)

unlike in wild-type mice, myotonic discharges are detected from anesthetized mice whose muscles are percussed or stretched (J:6814)

unlike in wild-type mice, myotonic discharges continue for several minutes after amputation (J:6814)

impaired muscle relaxation (J:14251)

mice exhibit myotonia

nervous systemaxon degeneration (J:6814)

by 225 days, mice exhibit degeneration of myelinated axons in the ventrolateral funiculus at all levels of the spinal cord

however, nerve roots and mixed peripheral nerves are not affected

growth/sizedecreased body weight (J:6814)

at 30 days mice weigh 10% less than wild-type mice and this difference increases to 40% in adulthood

reproductive systemreduced fertility (J:6814)

mice are not reliable breeders

skeletonkyphosis (J:6814)

Background Sensitivity: mice usually develop mild dorsal kyphosis on a mixed background

at day 80, mice exhibit thoracic kyphosis at the T3 to T5 level

Notes

This mutation arose spontaneously in the SWR/J strain. Homozygous mutant mice display classical myotonia similar to that described in human myotonic diseases. Homozygotes are recognizable at 2 weeks of age or earlier by prolonged stiff extension postures of the limbs when the cage is shaken or the mouse is dropped from about 10 cm. This behavior persists throughout life. When undisturbed, affected animals walk almost normally, but somewhat stiffly. They grow more slowly and weigh about 40% less than controls in adulthood. On an outbred background they may live a year or more and may be fertile. Electromyographic studies revealed changes characteristic of myotonia, i.e. repetitive firing at varying amplitude and frequency in all skeletal muscles tested. These discharges do not originate in peripheral nerves, and there is no evidence of muscle fiber necrosis (J:6814). This myotonia mutation was shown to be allelic to Clc1^adr (J:9721).

References

Original:	J:6814 Heller AH et al., "Myotonia, a new inherited muscle disease in mice." J Neurosci 1982 Jul;2(7):924-33
All:	8 reference(s)

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