Description

Strain Information

Former Names STOCK Eif2c2tm3.1Ghan/J    (Changed: 18-FEB-13 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N4+F4 (27-OCT-11) Generation Definitions   Donating Investigator Gregory Hannon,   Cold Spring Harbor Laboratory

Description
A point mutation in the Eif2c2 (eukaryotic translation initiation factor 2C, 2; also called Ago2) gene inactivates catalytic activity in this strain but does not disrupt gene expression. Homozygous neonates are anemic and die shortly after birth. Mice show a loss of miR-451, a small RNA important for erythropoiesis. Heterozygous targeted mutant mice are viable and fertile. There are no known phenotypic differences between the mouse carrying the floxed neo cassette (see Stock No. 14150) and this strain from which the cassette has been deleted. This strain may be useful in studies of microRNA biogenesis and erythropoiesis.

Development
An A to C mutation (D597A) was introduced to exon 14 and a loxP-flanked PGK-gb2-neo cassette (encoding neomycin/kanamycin resistance) was placed in intron 2. The point mutation creates an ADH rather than a DDH motif that disrupts catalytic activity, but not gene expression. The mutation was created in G4 (129S6/SvEvTac x C57BL/6Ncr)F1-derived embryonic stem cells. Crosses with a Sox2-cre strain on a mixed C57BL/6 and Swiss Webster background removed the floxed cassette. The strain was backcrossed to C57BL/6J for 3-4 generations by the donating laboratory.

Control Information

	Control
	+/+ from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ago2

016520	B6.129P2(129S4)-Ago2tm1.1Tara/J
014150	B6;129S6-Ago2tm3Ghan/J

View Strains carrying other alleles of Ago2     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ago2^tm3.1Ghan/Ago2^tm3.1Ghan

        involves: 129S6/SvEvTac * C57BL/6 * C57BL/6NCr * CBA * Swiss Webster

• mortality/aging
• complete neonatal lethality
  • mice die within hours of birth   (MGI Ref ID J:161968)
• hematopoietic system phenotype
• abnormal proerythroblast morphology
  • the number of proerythroblasts is increased 2- to 3-fold in the liver, bone marrow, and spleen compared with wild-type mice   (MGI Ref ID J:161968)
• decreased erythrocyte cell number
  • beginning at E18.5 and worsening after birth   (MGI Ref ID J:161968)
• integument phenotype
• pallor
  • after birth   (MGI Ref ID J:161968)

View Research Applications

Research Applications

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

Developmental Biology Research
Postnatal Lethality
      Homozygous

Hematological Research
Hematopoietic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ago2tm3.1Ghan
Allele Name		targeted mutation 3.1, Greggory J Hannon
Allele Type		Targeted (knock-in)
Common Name(s)		Ago2ADH; Ago2D598A;
Mutation Made By		Gregory Hannon,   Cold Spring Harbor Laboratory
Strain of Origin		(129S6/SvEvTac x C57BL/6NCr)F1
Promoter		Ago2, argonaute RISC catalytic subunit 2, mouse, laboratory
Molecular Note		Mice exhibit an A to C mutation that results in the amino acid substitution of alanine for aspartic acid at position 598 (D598A) within the catalytic DDH motif. A floxed neo cassette was removed by cre mediated recombination. [MGI Ref ID J:161968]

Genotyping

Genotyping Information

Genotyping Protocols

Eif2c2^tm3.1Ghan, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Cheloufi S; Dos Santos CO; Chong MM; Hannon GJ. 2010. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465(7298):584-9. [PubMed: 20424607]  [MGI Ref ID J:161968]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygotes die as neonates.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	+/+ from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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