In this targeted mutation strain, exons 11 through 17 are deleted. These Syx-/- mice exhibit mild neuropathy and defective endothelial cell junctions, and may be useful in studies of angiogenesis and autosomal recessive peripheral neuropathy.
Jay Baraban, Johns Hopkins University School of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Plekhg5 | pleckstrin homology domain containing, family G (with RhoGef domain) member 5 |
The protein encoded by the Plekhg5 (pleckstrin homology domain containing, family G (with RhoGef domain) member 5) gene activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in the human gene have been identified in patients presenting with recessive lower motor neuron disease or an intermediate form of Charcot-Marie-Tooth disease.
These mutant mice carry a targeted mutation in which exons 11 through 17, which encode the RhoGEF catalytic domain and a part of the PH domain, have been deleted. Mice that are homozygous for the targeted mutation are viable and fertile. While a truncated gene product (protein) is detected by Western blot analysis, no full length protein is detected. Homozygotes display abnormal secondary artery and capillary development with reduced coronary and renal capillary density. Endothelial cell junctions in homozygotes are defective, causing vascular leaking, edema and cardiac dysfunction. Homozygotes exhibit mild neuropathy, with diminished nerve conduction velocities.
During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
A targeting vector designed by Dr. Jay M. Baraban and Dr. Ruth Marx (John Hopkins University) was used to insert loxP sites flanking exons 11 to 17, which encode the catalytic domain. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. Heterozygous mice were crossed to transgenic mice (on the C57BL/6 genetic background) expressing Cre recombinase under the control of the CAG promoter to remove the floxed exons 11-17. The mice were then backcrossed to C57BL/6 for 10 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
Allele Name | targeted mutation 1.1, Jay Baraban |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Syx- |
Gene Symbol and Name | Plekhg5, pleckstrin homology domain containing, family G (with RhoGef domain) member 5 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 4 |
Molecular Note | LoxP sites flank the catalytic domain contained in exons 9-13. Germline cre expression results in excision of the floxed exons 9-13. Western blot analysis indicates the loss of full length protein. However, a truncated protein is present. |
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129(Cg)-Plekhg5tm1.1Jbar/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022785 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wildtype for Plekhg5<tm1.1Jbar> |
Frozen Mouse Embryo | B6.129(Cg)-Plekhg5<tm1.1Jbar>/J | $2595.00 |
Frozen Mouse Embryo | B6.129(Cg)-Plekhg5<tm1.1Jbar>/J | $2595.00 |
Frozen Mouse Embryo | B6.129(Cg)-Plekhg5<tm1.1Jbar>/J | $3373.50 |
Frozen Mouse Embryo | B6.129(Cg)-Plekhg5<tm1.1Jbar>/J | $3373.50 |
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