NF-HtailΔ mice lack the COOH-terminal of the Nefh (neurofilament, heavy polypeptide or NF-H) gene. These mice may be useful for studying the role of neurofilaments.
Dr. Don Cleveland, Ludwig Institute for Cancer Research (UCSD)
The Nefh (neurofilament, heavy polypeptide) gene encodes the heavy subunit of a neurofilament, a type IV intermediate (10 nm) filament protein. Neurofilaments function as the major cytoskeletal component in large myelinated axons of the peripheral nervous system. The heavy subunit contains 44-51 lysine-serine-proline repeats that are phosphorylated after neurofilament assembly. NF-HtailΔ mice contain a Myc epitope tag and neomycin cassette designed to replace 612 amino acids in the COOH terminus. Immunoblot analysis using an antibody raised against the COOH terminus of sciatic nerve extracts confirms the absence of NF-H protein in homozygous mice; heterozygous mice express 50-70% of the full length protein. NEFL (light subunit) and NEFM (medium subunit) levels are not affected by the mutation. Mice that are homozygous for the targeted mutation are viable and fertile with no overt phenotype. Loss of the NF-H tail does not affect neurofilament number, interfilament spacing, action potential speed, rate of neurofilament transport or the number of microtubules in axons. However, axons have fewer crossbridge spans between adjacent neurofilaments and some forked crossbridges. These mice may be useful for studying the role of neurofilaments.
The targeting vector was designed to replace 612 amino acids in the COOH terminal with a Myc epitope tag and a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6J for germline transmission. The strain was maintained on a mixed background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (000664) oocytes.
|Allele Name||targeted mutation 2, Don W Cleveland|
|Allele Type||Targeted (Not Applicable)|
|Allele Synonym(s)||Nefhtm2Dwc; targeted mutation 2, Don W Cleveland|
|Gene Symbol and Name||Nefh, neurofilament, heavy polypeptide|
|Gene Synonym(s)||NF200; NFH; Nfh; NF-H; mKIAA0845; Nfh; NEFH; CMT2CC|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||Sequence encoding the 612 carboxy terminal amino acids was deleted by a Myc-tagged neo cassette inserted by homologous recombination. Western blot analysis using antibodies directed toward the carboxy terminal and the Myc epitope tag showed the exclusive presence of truncated protein in sciatic and optic nerve extracts obtained from homozyous mutant mice.|
When maintaining a live colony, these mice are bred by homozygote sibling matings.
When using the B6;129-Nefhtm2Dwc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #032689 in your Materials and Methods section.
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