FVB;129-Sh3tc2^tm1.1Rchr/J

Stock number: 033933
Product name: Sh3tc2^deltaEx1
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Sh3tc2^ΔEx1 knock-in/knock-out mice have an EGFP replacing exon 1 of the SH3 domain and tetratricopeptide repeats 2 (Sh3tc2) gene abolishing endogenous gene expression. These mice may be useful for studying Charcot-Marie-Tooth disease type 4C, early-onset demyelinating form of peripheral neuropathy.

Detailed description

Sh3tc2^ΔEx1 knock-in/knock-out mice have an EGFP replacing exon 1 of the SH3 domain and tetratricopeptide repeats 2 (Sh3tc2) gene abolishing endogenous gene expression. This gene encodes an adapter or docking molecule expressed in Schwann cells that is localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and in regions of axoglial interactions. Mutations in SH3TC2 are associated with the onset of Charcot-Marie-Tooth disease type 4C (CMT4C), which is a demyelinating form of peripheral neuropathy. CMT4C is characterized by progressive scoliosis, delayed age of walking, muscular atrophy, distal weakness, and reduced nerve conduction velocity.

Sh3tc2^ΔEx1 homozygous mice develop progressive peripheral neuropathy manifested by decreased motor and sensory nerve conduction velocity beginning at 4 weeks and slowly worsening with age and hypomyelination of sciatic nerves near 2 months of age. The donating investigator states that homozygous mice have a mild peripheral nervous system abnormalities, such as abnormal clenching of toes and clasping of hind limbs upon tail suspension that start to develop at 4 weeks of age, yet they are viable, fertile, develop normally, and live as long as wildtype littermates. There is no detectable phenotype in heterozygous animals.

The donating investigator reports that EGFP fluorescence is detectable using immunohistochemistry, they did not extensively test if it is detectable by direct fluorescence.

Development

The Sh3tc2^neoΔEx1 targeting vector was designed to replace exon 1 of the SH3 domain and tetratricopeptide repeats 2 (Sh3tc2) gene with an enhanced green fluorescent protein sequence and a loxP flanked neomycin resistance (neo) cassette. The construct was electroporated into 129Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the chimeric mice were bred to Nestin-cre expressing mice on an FVB/N background to delete the neo cassette. Resulting offspring were crossed to remove the cre-expressing transgene, and Sh3tc2^ΔEx1 mice were subsequently bred together for more than 15 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ mice (Stock No. 001800) for at least one generation to establish the colony.

Allele

Symbol: Sh3tc2^tm1.1Rchr
Name: targeted mutation 1.1, Roman Chrast
MGI accession ID: MGI:4367025
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Sh3tc2^deltaEx1
Marker symbol: Sh3tc2
Marker name: SH3 domain and tetratricopeptide repeats 2
Marker synonyms: CMT4C; D430044G18Rik; MNMN; RGD1309038
Chromosome: 18
Strain of origin: 129/Sv
Site of expression: Schwann cells
Molecular note: Exon 1 was replaced with EGFP and a floxed neo cassette. Germ line, cre mediated recombination removes the neo cassette.