Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N5F1 (27-JAN-09)   Donating Investigator Brian Harfe,   University of Florida

Description
These mice contain loxP sites on either side of exon 23. Homozygous mice are viable and fertile with no gross phenotypic or behavioral abnormalities. Expression of the targeted allele is indistinguishable from wild-type despite the frt-flanked neomycin cassette. Cre-mediated recombination (resulting in deletion of exon 23) in the germline leads to developmental arrest at embryonic day 7.5 (E7.5). Tissue specific deletion has been shown to result in loss of microRNA (miRNA) processing. Mutant mice can be used to generate cell/tissue-specific deletions of the endogenous gene for applications in embryonic development, translation, protein processing and miRNA/siRNA regulation of gene expression.

For example, when crossed to a strain expressing Cre recombinase in mesenchyme (see Stock No. 005584), this mutant mouse strain may be useful in studies of limb morphogenesis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was used to flank exon 23 (encoding most of the second RNaseIII domain) of the endogenous gene with loxP sites. The vector also contained an frt-flanked neomycin resistance cassette between the exon and downstream loxP site. This construct was electroporated into "129" embryonic stem (ES) cells. Correctly targeted cells were injected into C57BL/6J blastocysts and chimeric mice were bred to C57BL/6J for germline transmission. Heterozygous offspring were bred to generate homozygotes. At some point, homozygotes were bred to mutant Gt(ROSA)26Sor mice on an unknown background. Upon arrival at The Jackson Laboratory, mice on the mixed genetic background were bred to select for the "Dicer-flox" allele and against the Gt(ROSA)26Sor reporter allele, resulting in Stock No. 006001. Mice from that colony were subsequently backcrossed to C57BL/6J for at least five generations to create these mice (Stock No. 006366).

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Dicer1^tm1Bdh allele

006001

STOCK Dicer1tm1Bdh/J

View Strains carrying   Dicer1^tm1Bdh     (1 strain)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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.

Dicer1^tm1Bdh/Dicer1^tm1Bdh Tg(Prrx1-cre)1Cjt/0

        involves: C57BL/6J * SJL/J   (conditional)

• limbs/digits/tail phenotype
• abnormal forelimb morphology (MGI Ref ID J:100475)
  • at E11 the forelimbs are smaller and at E12.5 the forelimb size resembles that of wild-type forelimbs at E11.5
  • starting at E10.5 increased cell death is seen in the limb mesoderm
• abnormal hindlimb morphology (MGI Ref ID J:100475)
  • the hindlimbs are smaller but not as severely affected as the forelimbs
  • starting at E12.5 increased cell death is seen in the limb mesoderm
• abnormal long bone morphology (MGI Ref ID J:100475)
  • the long bones of the arms and legs appear twisted
• oligodactyly (MGI Ref ID J:100475)
  • forelimbs show loss of digits and some fusion of digits
• skeleton phenotype
• abnormal long bone morphology (MGI Ref ID J:100475)
  • the long bones of the arms and legs appear twisted
• delayed endochondral bone ossification (MGI Ref ID J:100475)
  • bone formation from cartilage is delayed in the long bones of the limbs

Genes & Alleles

Gene & Allele Information

Allele Symbol		Dicer1tm1Bdh
Allele Name		targeted mutation 1, Brian D Harfe
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Dcrflox; Dicer1fl; Dicerflox;
Mutation Made By		Brian D. Harfe and Mike McManus,   UFlorida and UCSF
Gene Symbol and Name		Dicer1, Dicer1, Dcr-1 homolog (Drosophila)
Chromosome		12
Gene Common Name(s)		1110006F08Rik; D12Ertd7e; DCR1; DNA segment, Chr 12, ERATO Doi 7, expressed; Dicer; HERNA; KIAA0928; RIKEN cDNA 1110006F08 gene; mKIAA0928;
Molecular Note		A targeting vector was designed to insert loxP sites around the exon that encodes most of the second RNaseIII domain as well as an frt-flanked neo within the loxP-encompassed sequence. Cre-mediated removal of the sequence would result in the loss of 90 amino acids, a loss that does not create a downstream frame-shift or an unstable protein. [MGI Ref ID J:100475]

Genotyping

Genotyping Information

Genotyping Protocols

Dicer1^tm1Bdh, STD PCR, vers. 1

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Harfe BD; McManus MT; Mansfield JH; Hornstein E; Tabin CJ. 2005. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102(31):10898-903. [PubMed: 16040801]  [MGI Ref ID J:100475]

Additional References

Dicer1^tm1Bdh related

Calabrese JM; Seila AC; Yeo GW; Sharp PA. 2007. RNA sequence analysis defines Dicer's role in mouse embryonic stem cells. Proc Natl Acad Sci U S A 104(46):18097-102. [PubMed: 17989215]  [MGI Ref ID J:127467]

Chong MM; Rasmussen JP; Rundensky AY; Littman DR. 2008. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J Exp Med 205(9):2005-17. [PubMed: 18725527]  [MGI Ref ID J:138683]

Cuellar TL; Davis TH; Nelson PT; Loeb GB; Harfe BD; Ullian E; McManus MT. 2008. Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci U S A 105(14):5614-9. [PubMed: 18385371]  [MGI Ref ID J:133780]

Damiani D; Alexander JJ; O'Rourke JR; McManus M; Jadhav AP; Cepko CL; Hauswirth WW; Harfe BD; Strettoi E. 2008. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 28(19):4878-87. [PubMed: 18463241]  [MGI Ref ID J:135193]

Davis TH; Cuellar TL; Koch SM; Barker AJ; Harfe BD; McManus MT; Ullian EM. 2008. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 28(17):4322-30. [PubMed: 18434510]  [MGI Ref ID J:134779]

Friedman LM; Dror AA; Mor E; Tenne T; Toren G; Satoh T; Biesemeier DJ; Shomron N; Fekete DM; Hornstein E; Avraham KB. 2009. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc Natl Acad Sci U S A 106(19):7915-20. [PubMed: 19416898]  [MGI Ref ID J:148395]

Harris KS; Zhang Z; McManus MT; Harfe BD; Sun X. 2006. Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A 103(7):2208-13. [PubMed: 16452165]  [MGI Ref ID J:106072]

Hong X; Luense LJ; McGinnis LK; Nothnick WB; Christenson LK. 2008. Dicer1 is essential for female fertility and normal development of the female reproductive system. Endocrinology 149(12):6207-12. [PubMed: 18703631]  [MGI Ref ID J:142113]

Hornstein E; Mansfield JH; Yekta S; Hu JK; Harfe BD; McManus MT; Baskerville S; Bartel DP; Tabin CJ. 2005. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature 438(7068):671-4. [PubMed: 16319892]  [MGI Ref ID J:103424]

Kumar MS; Lu J; Mercer KL; Golub TR; Jacks T. 2007. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39(5):673-7. [PubMed: 17401365]  [MGI Ref ID J:123829]

Lynn FC; Skewes-Cox P; Kosaka Y; McManus MT; Harfe BD; German MS. 2007. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes 56(12):2938-45. [PubMed: 17804764]  [MGI Ref ID J:132315]

Maatouk DM; Loveland KL; McManus MT; Moore K; Harfe BD. 2008. Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79(4):696-703. [PubMed: 18633141]  [MGI Ref ID J:140872]

O'Rourke JR; Georges SA; Seay HR; Tapscott SJ; McManus MT; Goldhamer DJ; Swanson MS; Harfe BD. 2007. Essential role for Dicer during skeletal muscle development. Dev Biol 311(2):359-68. [PubMed: 17936265]  [MGI Ref ID J:127496]

Papaioannou MD; Pitetti JL; Ro S; Park C; Aubry F; Schaad O; Vejnar CE; Kuhne F; Descombes P; Zdobnov EM; McManus MT; Guillou F; Harfe BD; Yan W; Jegou B; Nef S. 2009. Sertoli cell Dicer is essential for spermatogenesis in mice. Dev Biol 326(1):250-9. [PubMed: 19071104]  [MGI Ref ID J:145178]

Pastorelli LM; Wells S; Fray M; Smith A; Hough T; Harfe BD; McManus MT; Smith L; Woolf AS; Cheeseman M; Greenfield A. 2009. Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome 20(3):140-51. [PubMed: 19169742]  [MGI Ref ID J:146873]

Soukup GA; Fritzsch B; Pierce ML; Weston MD; Jahan I; McManus MT; Harfe BD. 2009. Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Dev Biol 328(2):328-41. [PubMed: 19389351]  [MGI Ref ID J:149468]

Sugatani T; Hruska KA. 2009. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem 284(7):4667-78. [PubMed: 19059913]  [MGI Ref ID J:147602]

Zhou X; Jeker LT; Fife BT; Zhu S; Anderson MS; McManus MT; Bluestone JA. 2008. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205(9):1983-91. [PubMed: 18725525]  [MGI Ref ID J:138808]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, mutant mice can be bred to C57BL/6J or bred together to create a homozygous colony.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

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