Homozygous Lgi4^clp mice show, at birth or immediately thereafter, a postural deformity of one or both forelimbs in which the fingers are flexed; the wrist and shoulder may also be flexed, and the elbow may be rotated inward (the "waiter's tip" posture). The joints can be moved passively, though much later in life the distal ones may become fixed, probably secondary to inactivity. Affected limbs are also weak. The most obvious defect on microscopic examination is a generalized delay in myelination, and a persistence of some axons and Schwann cells in the "promyelin" configuration throughout life, a state never seen in the normal peripheral nervous system. Peripheral axons appear to grow to a larger caliber before myelination begins in Lgi4^clp /Lgi4^clp mice than in +/? mice. In some animals, the ratio of myelin sheath thickness to axon caliber is reduced. The histopathological abnormalities are remarkably uniform throughout the entire peripheral nervous system and do not correlate well with the postural abnormalities and weakness, which are often much more severe in one forelimb than the other, and are always much more evident in the forelimbs than the hindlimbs

Development

The claw paw mutation arose spontaneously in the B6.Cg-Lep^ob/J strain at The Jackson Laboratory in1977. The obese mutation was bred out by backcross-intercross to C57BL/6J and this mutant subline was subsequently maintained by sibling intercrossing either homozygote x heterozygote or heterozygote x heterozygote. In 1984 embryos were generated for cryopreservation from heterozygous males and C57BL/6J females.

Control Suggestions

Untyped from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Lgi4^clp

Allele Symbol: Lgi4^clp

Allele Name	claw paw
Allele Type	Spontaneous (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Lgi4, leucine-rich repeat LGI family, member 4
Gene Synonym(s)
Strain of Origin	B6.Cg-Lep^ob/J
Chromosome	7
General Note	This mutation arose at The Jackson Laboratory in 1977. The pathology of homozygous mutant mice differs from other myelin deficient mutants in that there is no obvious increase in Schwann cells and that the axons that persist in promyelin fibers are smaller (J:11392).
Molecular Note	A CTCT repeat located six base pairs 5' to exon 4 is replaced with a 225-bp repetitive sequence which is 100% homologous to a repeat element located 797 bp upstream. This interferes with the third intron 3' splice site resulting in exon3 spliced to exon 5. The resulting protein, lacking exon 4, is not secreted as is the wild-type allele.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Lgi4^clp related

Neurobiology Research
- Myelination Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Lgi4^clp/Lgi4^clp
involves: C57BL/6J * FVB/N

nervous system phenotype

abnormal myelination
- cultures of primary sensory neurons fail to myelinate

The following phenotype relates to a compound genotype created using this strain

Genotype: Lgi4^clp/Lgi4^clp
C57BL/6J-Lgi4/J

growth/size/body region phenotype

decreased body size
- adults with forelimb abnormalities are almost always smaller than controls

limbs/digits/tail phenotype

abnormal limb morphology
- abnormally flexed joints can be extended early in life but fixed contractures often develop with age
- exhibit an arthrogryposis-like phenotype affecting the forelimbs, and in severe cases, also the hindlimbs

abnormal forelimb morphology
- flexed forelimbs (fingers, wrists, shoulders), elbows rotated inwards
- forelimbs with abnormal postures are held flexed at one or more of the shoulder, wrist or digital joints but extended at the elbow, resulting in the forelimbs being pointed toward the hindlimbs

abnormal hindlimb morphology
- hindlimbs are more subtly affected than forelimbs, with the most common abnormality a mild, usually symmetrical, weakness of hindpaw dorsiflexion

abnormal digit morphology
- fingers are flexed

decreased diameter of radius
- radii are thinner and somewhat straighter than in controls, however gross bony landmarks and sections through bones and joints appear normal

decreased diameter of ulna
- ulnae are thinner and somewhat straighter than in controls

mammalian phenotype

muscle phenotype
- Normal - do not exhibit any histological abnormalities in skeletal muscle or any reductions in large limb muscle mass

mortality/aging

postnatal lethality, incomplete penetrance
- homozygotes with severe forelimb abnormalities often die within 2 to 3 days after birth due to difficulties in positioning themselves for suckling and thus do not get enough nourishment, however if they do survive the first few weeks, their condition usually begins to improve and some have a relatively normal lifespan
- lly begins to improve and some have a relatively normal lifespan

behavior/neurological phenotype

abnormal maternal nurturing
- maternal abilities are rarely good in females with severe forelimb abnormalities

abnormal posture
- abnormal forelimb joint postures seen within 1-2 days after birth
- postural deformity (waiter's tip posture) of one or both forelimbs in which the fingers are flexed and the wrist and shoulder may also be flexed and the elbow rotated inward

impaired righting response
- unable to extend an affected forelimb above the head as part of a righting response when turned from its back onto one side

abnormal locomotor behavior
- develop a more pronounced waddle as grow older
- homozygotes with bilateral forelimb abnormalities have a difficult time from a very young age in moving around the cage and slither around the cage on the undersurface of their muzzles

abnormal sexual interaction
- males breed poorly, however females are able to breed successfully

nervous system phenotype

abnormal nervous system morphology
- exhibit a variable increase in peripheral nerve fasciculation and an occasional mild increase in endoneural connective tissue, however no differences in the number of Schwann cells or any evidence of denervation atrophy
- all peripheral nerves are hypotrophic

abnormal myelin sheath morphology
- in some mutants, the ratio of myelin sheath thickness to axon caliber is reduced
- variable degree of generalized hypomyelination, with peripheral myelin sheaths thinner relative to axonal size than in controls

abnormal myelination
- delay in myelination and a persistence of some axons and Schwann cells in the promyelin configuration throughout life
- failure of myelination in some fibers leads to persistent promyelin fibers with small axons, especially in muscles that normally have small axons
- all homozygotes have delayed and abnormal myelination of the peripheral nervous system but not the central nervous system

abnormal sciatic nerve morphology
- hypertrophy of the sciatic nerve

abnormal axon morphology
- the axons that are enclosed by promyelin fibers have smaller axon calibers than those of myelinated fibers

skeleton phenotype

decreased diameter of radius
- radii are thinner and somewhat straighter than in controls, however gross bony landmarks and sections through bones and joints appear normal

abnormal long bone morphology

decreased diameter of ulna
- ulnae are thinner and somewhat straighter than in controls

Genotype: Lgi4^clp/Lgi4^clp
involves: C57BL/6J

nervous system phenotype

demyelination
- in the sciatic nerve at P12

References

Additional References

Henry EW; Eicher EM; Sidman RL. 1991. The mouse mutation claw paw: forelimb deformity and delayed myelination throughout the peripheral nervous system. J Hered 82(4):287-94PubMed: 1652607 MGI: J:11392

Additional - Lgi4^clp related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Lgi4
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664).
- Additional Breeding and Husbandry Support
Citation
When using the claw paw mouse strain in a publication, please cite the originating article(s) and include JAX stock #000974 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Lgi4<clp>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:claw paw

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Lgi4clp

Allele Symbol: Lgi4clp

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Lgi4clp related

Mammalian Phenotype Terms by Genotype

Genotype: Lgi4clp/Lgi4clpinvolves: C57BL/6J * FVB/N

nervous system phenotype

Genotype: Lgi4clp/Lgi4clpC57BL/6J-Lgi4/J

growth/size/body region phenotype

limbs/digits/tail phenotype

mammalian phenotype

mortality/aging

behavior/neurological phenotype

nervous system phenotype

skeleton phenotype

Genotype: Lgi4clp/Lgi4clpinvolves: C57BL/6J

nervous system phenotype

References

Additional References

Additional - Lgi4clp related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Lgi4^clp

Allele Symbol: Lgi4^clp

Genotype: Lgi4^clp related

Genotype: Lgi4^clp/Lgi4^clp
involves: C57BL/6J * FVB/N

Genotype: Lgi4^clp/Lgi4^clp
C57BL/6J-Lgi4/J

Genotype: Lgi4^clp/Lgi4^clp
involves: C57BL/6J

Additional - Lgi4^clp related