Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129-Srftm1Ddg/J    (Changed: 03-JAN-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N8+N2pN1 Generation Definitions   Donating Investigator David D. Ginty,   Johns Hopkins University

Description
These mice possess loxP sites that flank promoter and exon 1 sequences. Mice that are homozygous for this allele are viable and fertile. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. Excision of the floxed fragment results in the removal of key regulatory elements and many of the DNA-binding and dimerization residues of the gene.

When bred to a strain expressing Cre recombinase under the control of mouse transgelin promoter (see Stock No. 004746 for example), this mutant mouse strain may be useful in studies of cardiovascular disease.

Development
loxP sites were inserted 1.4 kb upstream and 1.1 kb downstream of the transcription start site, resulting in floxed promoter and exon 1 sequences. The construct was electroporated into 129/Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric animals were crossed with C57BL/6.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Srf^tm1Rmn/Srf^tm1Rmn Tg(Tagln-cre)1Jomm/0

        involves: CD-1   (conditional)

• mortality/aging
• complete embryonic lethality during organogenesis
  • no viable embryos are found after E11.5   (MGI Ref ID J:94725)
• cardiovascular system phenotype
• abnormal myocardial fiber morphology
  • the sarcomeres and Z disks are disorganized and the myofilaments are disarrayed   (MGI Ref ID J:94725)
• vascular smooth muscle hypotrophy
  • a 35% decrease in smooth muscle cells at the dorsal aspect of the aorta is found   (MGI Ref ID J:94725)
• muscle phenotype
• abnormal myocardial fiber morphology
  • the sarcomeres and Z disks are disorganized and the myofilaments are disarrayed   (MGI Ref ID J:94725)
• vascular smooth muscle hypotrophy
  • a 35% decrease in smooth muscle cells at the dorsal aspect of the aorta is found   (MGI Ref ID J:94725)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Srftm1Rmn
Allele Name		targeted mutation 1, Narendrakumar Ramanan
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Srff; Srffl; Srftm1Ddg; Srftm1Jomm;
Mutation Made By		Narendrakumar Ramanan,   Johns Hopkins
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Srf, serum response factor
Chromosome		17
Gene Common Name(s)		AW049942; AW240594; MCM1; RGD1559787; expressed sequence AW049942; expressed sequence AW240594;
Molecular Note		LoxP sites were inserted to flank the promoter and exon 1, the region containing key regulatory elements important for promoter activity as well as many of the DNA-binding and dimerization residues. [MGI Ref ID J:94725] [MGI Ref ID J:99232]

Genotyping

Genotyping Information

Genotyping Protocols

Srf^tm1Rmn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Miano JM; Ramanan N; Georger MA; de Mesy Bentley KL; Emerson RL; Balza RO Jr; Xiao Q; Weiler H; Ginty DD; Misra RP. 2004. Restricted inactivation of serum response factor to the cardiovascular system. Proc Natl Acad Sci U S A 101(49):17132-7. [PubMed: 15569937]  [MGI Ref ID J:94725]

Additional References

Ramanan N; Shen Y; Sarsfield S; Lemberger T; Schutz G; Linden DJ; Ginty DD. 2005. SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci 8(6):759-67. [PubMed: 15880109]  [MGI Ref ID J:99232]

Srf^tm1Rmn related

Balza RO Jr; Misra RP. 2006. Role of the serum response factor in regulating contractile apparatus gene expression and sarcomeric integrity in cardiomyocytes. J Biol Chem 281(10):6498-510. [PubMed: 16368687]  [MGI Ref ID J:110312]

Halene S; Gao Y; Hahn K; Massaro S; Italiano JE Jr; Schulz V; Lin S; Kupfer GM; Krause DS. 2010. Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood 116(11):1942-50. [PubMed: 20525922]  [MGI Ref ID J:164524]

Holtz ML; Misra RP. 2008. Endothelial-specific ablation of serum response factor causes hemorrhaging, yolk sac vascular failure, and embryonic lethality. BMC Dev Biol 8:65. [PubMed: 18570667]  [MGI Ref ID J:139204]

Holtz ML; Misra RP. 2011. Serum response factor is required for cell contact maintenance but dispensable for proliferation in visceral yolk sac endothelium. BMC Dev Biol 11:18. [PubMed: 21401944]  [MGI Ref ID J:171452]

Johnson AW; Crombag HS; Smith DR; Ramanan N. 2011. Effects of serum response factor (SRF) deletion on conditioned reinforcement. Behav Brain Res 220(2):312-8. [PubMed: 21329726]  [MGI Ref ID J:171461]

Lu PP; Ramanan N. 2012. A critical cell-intrinsic role for serum response factor in glial specification in the CNS. J Neurosci 32(23):8012-23. [PubMed: 22674276]  [MGI Ref ID J:185185]

Lu PP; Ramanan N. 2011. Serum response factor is required for cortical axon growth but is dispensable for neurogenesis and neocortical lamination. J Neurosci 31(46):16651-64. [PubMed: 22090492]  [MGI Ref ID J:177911]

Newbern J; Zhong J; Wickramasinghe RS; Li X; Wu Y; Samuels I; Cherosky N; Karlo JC; O'Loughlin B; Wikenheiser J; Gargesha M; Doughman YQ; Charron J; Ginty DD; Watanabe M; Saitta SC; Snider WD; Landreth GE. 2008. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A 105(44):17115-20. [PubMed: 18952847]  [MGI Ref ID J:144862]

Ramanan N; Shen Y; Sarsfield S; Lemberger T; Schutz G; Linden DJ; Ginty DD. 2005. SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat Neurosci 8(6):759-67. [PubMed: 15880109]  [MGI Ref ID J:99232]

Smith EC; Thon JN; Devine MT; Lin S; Schulz VP; Guo Y; Massaro SA; Halene S; Gallagher P; Italiano JE Jr; Krause DS. 2012. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood 120(11):2317-29. [PubMed: 22806889]  [MGI Ref ID J:189155]

Smith-Hicks C; Xiao B; Deng R; Ji Y; Zhao X; Shepherd JD; Posern G; Kuhl D; Huganir RL; Ginty DD; Worley PF; Linden DJ. 2010. SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. Nat Neurosci 13(9):1082-9. [PubMed: 20694003]  [MGI Ref ID J:165284]

Sullivan AL; Benner C; Heinz S; Huang W; Xie L; Miano JM; Glass CK. 2011. Serum response factor utilizes distinct promoter- and enhancer-based mechanisms to regulate cytoskeletal gene expression in macrophages. Mol Cell Biol 31(4):861-75. [PubMed: 21135125]  [MGI Ref ID J:170425]

Verdoni AM; Ikeda S; Ikeda A. 2010. Serum response factor is essential for the proper development of skin epithelium. Mamm Genome 21(1-2):64-76. [PubMed: 20047077]  [MGI Ref ID J:156871]

Verdoni AM; Schuster KJ; Cole BS; Ikeda A; Kao WW; Ikeda S. 2010. A pathogenic relationship between a regulator of the actin cytoskeleton and serum response factor. Genetics 186(1):147-57. [PubMed: 20610412]  [MGI Ref ID J:164255]

Vialou V; Maze I; Renthal W; LaPlant QC; Watts EL; Mouzon E; Ghose S; Tamminga CA; Nestler EJ. 2010. Serum response factor promotes resilience to chronic social stress through the induction of DeltaFosB. J Neurosci 30(43):14585-92. [PubMed: 20980616]  [MGI Ref ID J:166519]

Wickramasinghe SR; Alvania RS; Ramanan N; Wood JN; Mandai K; Ginty DD. 2008. Serum response factor mediates NGF-dependent target innervation by embryonic DRG sensory neurons. Neuron 58(4):532-45. [PubMed: 18498735]  [MGI Ref ID J:145293]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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