Strain Name:
B6;129P2-Mllt6Gt(AC0433)Wtsi/Mmucd
Stock Number:
036920-UCD
Citation ID:
RRID:MMRRC_036920-UCD
Other Names:
Af17-/-

Strain Information

Mllt6Gt(AC0433)Wtsi
Name: myeloid/lymphoid or mixed-lineage leukemia; translocated to, 6; gene trap AC0433, Wellcome Trust Sanger Institute
Synonyms: Af17-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 11
Alteration at locus: Gene Trap
Mllt6
Name: myeloid/lymphoid or mixed-lineage leukemia; translocated to, 6
Synonyms: Af17
Type: Gene
Species: Mouse
Chromosome: 11
Alteration at locus: Gene Trap
NCBI: 246198
HGNC: HGNC:7138
Homologene: 31347
Genetic Alterations
The gene trap vector carrying beta-geo reporter (pGT0lxr) was inserted into intron 7. The insertion disrupts Af17 mRNA splicing between exon 7 and 8, presumably leading to deletion of Af17 aa 256-1079 and generation of a hybrid protein harboring Af17 aa 1-255 fused in-frame with beta-geo reporter. Thereby, the fusion protein expression is under control of the endogenous Af17 promoter, allowing determination of Af17 expression profile by X-gal staining. Furthermore, the insertion is also expected to remove most, if not all, of the Af17 function. In particular, the hybrid protein harbors the PHD finger (aa 8-58), but is not anticipated to bind Dot1a because it lacks the Dot1a-interacting domain (aa 635-786).
ES Cell Line
E14TG2a.4 derived from 129P2/OlaHsd
Phenotype

Homozygous: Homozygous mutant mice are viable, fertile, normal in size, and do not display any gross physical, behavioral, or hematopoietic abnormalities. Compared with wild-type mice, Af17-deficient mice had lower BP (11 mmHg), higher urine volume, and increased sodium excretion despite mildly increased plasma concentrations of aldosterone. Deletion of Af17 led to increased dimethylation of histone H3 K79 and reduced ENaC (epithelial Na+ channel) subunitfunction. The attenuated function of ENaC resulted from decreased ENaC mRNA and protein expression, fewer active channels, lower open probability, and reduced effective activity. In contrast, inducing high levels of plasma aldosterone by a variety of methods completely compensated for Af17 deficiency with respect to sodium handling and BP. Af17-mediated regulation of BP is largely, but not exclusively, the result of modulating ENaC, suggesting it has potential as a therapeutic target for the control of BP.

Heterozygous: Same as wild-type.

Mammalian Phenotype Terms
Allelic Composition: Mllt6Gt(AC0433)Wtsi/Mllt6Gt(AC0433)Wtsi (Genetic Background: involves: 129P2/OlaHsd * C57BL/6 )

MeSH Terms
  • Animals
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Embryonic Development/genetics
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Hematopoiesis/genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid-Lymphoid Leukemia Protein/genetics
  • Myeloid-Lymphoid Leukemia Protein/metabolism
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism
  • Phenotype
  • Aldosterone/blood
  • Blood Pressure/drug effects
  • Blood Pressure/physiology
  • DNA-Binding Proteins/deficiency
  • DNA-Binding Proteins/physiology
  • Epithelial Sodium Channels/physiology
  • Histones/metabolism
  • Homeostasis/drug effects
  • Homeostasis/physiology
  • Kidney/drug effects
  • Kidney/physiology
  • Models, Animal
  • Neoplasm Proteins/deficiency
  • Neoplasm Proteins/physiology
  • Potassium, Dietary/pharmacology
  • Sodium/urine
  • Sodium, Dietary/pharmacology
Strain Development
Af17 mutant mice were created by using an existing gene trap SIGTR ES cell line AC0433 (MMRRC:020107-UCD) available at MMRRC. The ES clone was used to generate chimera mice. Chimeric animals were crossed with C57BL/6 mice to generate F1 offspring. The litter mates of the F1 offsprings were crossed to generate Af17-/- mice. The litter mates of Af17-/- were crossed for at least 20 generations.
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@ucdavis.edu. Older strains may not have this information.
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Models for Human Disease
  • Research Tools
Donor
Wenzheng Zhang, Ph.D., University of Texas Medical School at Houston.
Primary Reference

Zhang Z, Huang L, Reisenauer MR, Wu H, Chen L, Zhang Y, Xia Y, Zhang W. Widely expressed Af17 is likely not required for embryogenesis, hematopoiesis, and animal survival. Genesis. 2010 Dec;48(12):693-706. (Medline PMID: 21170927).

Chen L, Wu H, Pochynyuk OM, Reisenauer MR, Zhang Z, Huang L, Zaika OL, Mamenko M, Zhang W, Zhou Q, Liu M, Xia Y, Zhang W. Af17 deficiency increases sodium excretion and decreases blood pressure. J Am Soc Nephrol. 2011 Jun;22(6):1076-86. (Medline PMID: 21546577)

Colony and Husbandry Information

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.
Coat Color
Brown
MMRRC Breeding System
Sib-mating
Breeding Scheme(s)

Wild-type female x Heterozygous male littermate or reciprocal mating

Homozygous female x Homozygous male littermate

Generation
F20
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
5-9
Recommended wean age
3 weeks

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Distribution of this strain requires execution of the Sanger Institute Gene Trap Resource Letter of Agreement. A link to this form will be provided via email when an order is submitted; the PDF form should be downloaded or the email forwarded to the appropriate institutional representative for completion following directions in the document.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
036920-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
036920-UCD-SPERM Cryo-preserved spermatozoa $546.25 / Non-Profit Aliquot Approximate quantity3
036920-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.