These Syt7 knock-out mice exhibit enhanced accumulations of connective tissue elements in skeletal muscle and skin with elevated levels of serum creatine kinase.
Norma Andrews, Yale University School of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Syt7 | synaptotagmin VII |
At birth, mice homozygous for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although Northern analysis fails to detect full-length transcripts, two minor alternatively spliced (alpha and beta) isoforms are generated. Protein product is not detected. Reproductive capacity appears to decline faster in mutant mice. The average litter size in +6 month-old mice is ~3 in mutants compared to ~7 in wild type mice. Lysosomal exocytosis and plasma membrane resealing in response to membrane wounding is impaired in mouse embryo fibroblasts derived from mutants. Histological analysis of mutants 14 weeks of age indicates that most tissues appear normal with the exception of enhanced accumulations of connective tissue elements, indicative of fibrosis, in skeletal muscle and skin. Examination of skeletal muscle from younger animals (4 weeks of age) reveals evidence of fiber degeneration and inflammation. Strong anti-nuclear antibody response is detected in serum at 19 and 44 weeks of age, but not in 8-week-old animals. Elevated levels of serum creatine kinase, a diagnostic marker for muscle fiber injury, are also observed. Decreased forelimb grip is observed in mutant mice more than 19 weeks of age. This mutant strain may be useful in studies examining the mechanisms of membrane homeostasis, secretion and autoimmunity.
A targeting vector containing a loxP-flanked neomycin resistance was used to disrupt exons 4-5 of the targeted gene. This region encodes the C2A calcium binding domain. The construct was electroporated into 129S1/Sv-p+ Tyr+ KitlSl-J/+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
Allele Name | targeted mutation 1, Norma W Andrews |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Syt VII - |
Gene Symbol and Name | Syt7, synaptotagmin VII |
Gene Synonym(s) | |
Strain of Origin | 129S1/Sv-Oca2+ Tyr+ Kitl+ |
Chromosome | 19 |
Molecular Note | A loxP flanked neomycin resistance cassette replaced most of exon 4 and exon 5. In the process a stop codon was generated in exon 4 after the codon for amino acid 83. Absence of the 1.2kb mRNA for the major isoform of this gene was established by Northern blot analysis. Lack of protein product was confirmed by Western blot analysis. However, a truncated protein may be produced. |
Mutations Made By | Norma Andrews, Yale University School of Medicine |
This strain originated on a B6;129S1 background and has been backcrossed to C57BL/6 for 7 generations before being made homozygous. When maintained in a live colony, this strain is maintained by homozygous matings.
When using the Syt VII KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004950 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Syt7<tm1Nan> |
Frozen Mouse Embryo | B6.129S1-Syt7<tm1Nan>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S1-Syt7<tm1Nan>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6.129S1-Syt7<tm1Nan>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6.129S1-Syt7<tm1Nan>/J Frozen Embryos | $3373.50 |
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