Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N7F?+N1+N1p (11-SEP-05)   Donating Investigator Norma Andrews,   Yale University School of Medicine

Description
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.

Development
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⁺ Kitl^Sl-J/+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Syt7

006388	B6;129-Syt7tm1Sud/J
006389	B6;129-Syt7tm2Sud/J

View Strains carrying other alleles of Syt7     (2 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Syt7^tm1Nan/Syt7^tm1Nan

        involves: 129S1/Sv * C57BL/6

• cellular phenotype
• abnormal cell physiology (MGI Ref ID J:85201)
  • embryo fibroblasts are resistant to invasion by Trypanosoma cruzi
  • failure of exocytosis and wound resealing in embryo fibroblasts
• immune system phenotype
• increased anti-nuclear antigen antibody level (MGI Ref ID J:85201)
  • antinuclear antibody response in serum by 19 weeks
• increased inflammatory response (MGI Ref ID J:85201)
• myositis (MGI Ref ID J:85201)
  • extensive endomysial cellular infiltration at week 4
  • week 8, scattered foci of inflammation
  • invasion of degenerating muscle fibers by macrophages and eosinophiles
  • inflammatory cells less abundant as mice age but fibrosis detectable until week 44
• increased susceptibility to autoimmune disorder (MGI Ref ID J:85201)
  • similarities to human autoimmune polymyositis/dermatositis
• muscle phenotype
• abnormal skeletal muscle morphology (MGI Ref ID J:85201)
  • extensive endomysial cellular infiltration at 4 weeks
  • by 8 weeks, mast cells and bundles of collagen fibers found in endomysial space
  • fiber degeneration
• skeletal muscle interstitial fibrosis (MGI Ref ID J:85201)
• muscle weakness (MGI Ref ID J:85201)
  • decreased forelimb grip strength after 19 weeks
• myositis (MGI Ref ID J:85201)
  • extensive endomysial cellular infiltration at week 4
  • week 8, scattered foci of inflammation
  • invasion of degenerating muscle fibers by macrophages and eosinophiles
  • inflammatory cells less abundant as mice age but fibrosis detectable until week 44
• reproductive system phenotype
• abnormal fertility/fecundity (MGI Ref ID J:85201)
  • reproductive capacity declines faster with age (litters of 3 at 6 months as opposed to 7 for wild-type mice)
  • normal fertility otherwise
• other phenotype
• fibrosis (MGI Ref ID J:85201)
  • enhanced accumulation of connective tissue elements seen histologically in the skin and skeletal muscle (fibrosis)
  • increased collagen deposition not seen in other tissues

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Syt7^tm1Nan related

Immunology and Inflammation Research
Autoimmunity (anti-nuclear antibodies)
Inflammation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Syt7tm1Nan
Allele Name		targeted mutation 1, Norma W Andrews
Allele Type		Targeted (knock-out)
Common Name(s)		Syt VII -;
Mutation Made By		Norma Andrews,   Yale University School of Medicine
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Syt7, synaptotagmin VII
Chromosome		19
Gene Common Name(s)		AI851541; B230112P13Rik; IPCA-7; MGC150517; PCANAP7; RIKEN cDNA B230112P13 gene; SYT-VII; expressed sequence AI851541;
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. [MGI Ref ID J:85201]

Genotyping

Genotyping Information

Genotyping Protocols

Syt7^tm1Nan, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Chakrabarti S; Kobayashi KS; Flavell RA; Marks CB; Miyake K; Liston DR; Fowler KT; Gorelick FS; Andrews NW. 2003. Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice. J Cell Biol 162(4):543-9. [PubMed: 12925704]  [MGI Ref ID J:85201]

Additional References

Syt7^tm1Nan related

Chan WT; Sherer NM; Uchil PD; Novak EK; Swank RT; Mothes W. 2008. Murine leukemia virus spreading in mice impaired in the biogenesis of secretory lysosomes and Ca2+-regulated exocytosis. PLoS ONE 3(7):e2713. [PubMed: 18629000]  [MGI Ref ID J:139279]

Czibener C; Sherer NM; Becker SM; Pypaert M; Hui E; Chapman ER; Mothes W; Andrews NW. 2006. Ca2+ and synaptotagmin VII-dependent delivery of lysosomal membrane to nascent phagosomes. J Cell Biol 174(7):997-1007. [PubMed: 16982801]  [MGI Ref ID J:115013]

Zhao H; Ito Y; Chappel J; Andrews NW; Teitelbaum SL; Ross FP. 2008. Synaptotagmin VII regulates bone remodeling by modulating osteoclast and osteoblast secretion. Dev Cell 14(6):914-25. [PubMed: 18539119]  [MGI Ref ID J:137198]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	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.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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