C57BL/6J-Lgi4^clp/J

Stock number: 000974
Product name: claw paw
Research areas: Neurobiology Research

Description

These mice carry a spontaneous mutation at the Lgi4 locus characterized by a postural deformity of one or both forelimbs.

Detailed description

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.

Allele

Symbol: Lgi4^clp
Name: claw paw
MGI accession ID: MGI:1856594
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Lgi4
Marker name: leucine-rich repeat LGI family, member 4
Marker synonyms: AMC1; AMCNMY; clp; LGIL3
Chromosome: 7
Strain of origin: B6.Cg-Lep^ob/J
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.
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).