B6.129-Klc1^tm1Gsn/J

Stock number: 004098
Product name: KLC1 KO
Research areas: Developmental Biology Research, Neurobiology Research

Description

These Klc1 knock-out mice exhibit motor disabilities and perinatal mortality.

Detailed description

The donating investigator indicates that mice that are homozygous for the targeted allele on a C57BL/6 genetic background exhibit significant perinatal mortality (60%). Mortality seems not to be a factor on a mixed B6;129 background. Surviving mice are noticeably smaller than wildtype mice. Mice surviving to adulthood breed poorly, possibly due to less than adequate nurturing capabilities. Minor amounts of a functionless, truncated protein product can be detected. Motor defects are evident, as are alterations in intracellular localization of kinesin-I and COP-I components.

Development

A targeting vector containing an IRES/beta-geo cassette was used to disrupt a portion of the targeted gene encoding the conserved TPR region. The construct was electroporated into 129X1/SvJ x 129S1/Sv-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for at least six generations (6/01).

Allele

Symbol: Klc1^tm1Gsn
Name: targeted mutation 1, Lawrence S B Goldstein
MGI accession ID: MGI:2136259
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Klc1
Marker name: kinesin light chain 1
Chromosome: 12
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Molecular note: An IRES Beta-geo cassette replaced the exon that encodes the entire first TPR domain and part of the second TPR domain. Western analysis of crude cytoplasmic brain extracts of homozygous mutant mice detected dramatically reduced levels of full length KLC1, as well as very small amounts of truncated KLC1. Immunoprecipitation studies did not detect either form of KLC1 in KIF5A or KIF5B coprecipitates of brain extracts of homozygous mutant mice. Immunofluorescence studies of sensory and motor neuron cell bodies in dorsal root ganglion and spinal cord of homozygous mutant mice detected very faint KCL1 staining.