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Strain Detail Sheet

Strain Name:
C57BL/6J-Ank1M1Btlr/Mmmh
Stock Number:
037103-MU
Citation ID:
RRID:MMRRC_037103-MU
Other Names:
hema6
Major Collection:
Beutler Mutagenetix

Strain Information

Gene Details

Ank1M1Btlr
Name: ankyrin 1, erythroid; mutation 1, Bruce Beutler
Synonyms: hema6
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Chemically Induced
Ank1
Name: ankyrin 1, erythroid
Synonyms: Ank-1, pale
Type: Gene
Species: Mouse
Chromosome: 8
Alteration at locus: Chemically Induced
NCBI: 11733
HGNC: HGNC:492
Homologene: 55427

Additional Resources
IMPC
Google
Entrez
PubMed
IMSR
Gene Ontology
BioGPS
Gene Cloud
IGTC
Mouse Phenome DB
Mouse Mine
KOMP Phenotyping
Monarch
GeneCards
ClinGen
Genetic Alterations
The Ank1 mutation in the index hema6 mouse was identified as a T to C transition at position 24,145,986 bp on chromosome 8 corresponding to base pair 122,756 of the genomic DNA sequence of Ank1 (NC_000074). The hema6 mutation is within intron 13,791 nucleotides from exon 13 and 209 nucleotides from exon 14 (of 44 total exons). In contrast to the single 400 base pair band detected in the wild-type sample, three major cDNA fragments were detected in the hema6 homozygotes: one corresponded to the size of wild-type Ank1 transcript, two additional fragments were observed at a higher molecular weight. The long splicing isoform contained a cryptic exon of 317 base pair as a result of the use of a preexisting 3’ splice site that is 108 base pair upstream from the hema6 mutation. The short splicing isoform incorporated two cryptic exons as a result of the use of the aforementioned 3’ splice site as well as two preexisting 5’ and 3’ splice sites downstream of the hema6 mutation. Both mutant transcripts introduced an in-frame stop codon that would result in truncation of the protein eight amino acids after residue 501; full-length aberrant mRNA was not detected, indicating nonsense-mediated decay of the mutant transcript occurred.
Genotype Determination

Strain Description

Phenotype

Homozygous: The index hema6 mouse had reduced mean corpuscular volume (MCV) and MCV hemoglobin, but increased red blood cell counts. Homozygous hema6 mice showed microcytosis and spherocytosis of RBCs. Stomatocytes , spherocytes, and membrane blebbing of erythrocytes from homozygote hema6 mice. Serum erythropoietin levels were slightly elevated in homozygous hema6 mice at 8 weeks compared to the wild-type control. Mild reticulocytosis was observed in homozygous hema6 mice. RBCs from hema6 homozygous mice exhibited increased hemolysis. The half-life of the RBCs in the homozygous hema6 mice was approximately 18 days compared with 28 days in the wild-type controls. Histological examination found that the spleens from hema6 homozygous mice were enlarged compared to the wild-type controls and displayed some effacement.The spleens from homozygous animals had increased sequestration and destruction of abnormal RBCs as indicated by excessive iron deposits. The RBCs from hema6 homozygous mice exhibited increased osmotic fragility compared to those in wild-type mice. Some hema6 homozygous mice exhibited an anemia that worsened with age. Erythroid progenitors from bone marrow were reduced in homozygous hema6 mice compared to wild-type.

Heterozygous: Erythroid progenitors from bone marrow were reduced in heterozygous hema6 mice compared to wild-type. RBCs from hema6 heterozygous mice exhibited increased hemolysis. The RBCs from hema6 heterozygous mice exhibited increased osmotic fragility compared to those in wild-type mice.

Mammalian Phenotype Terms
Allelic Composition: Ank1M1Btlr/Ank1M1Btlr (Genetic Background: C57BL/6J-Ank1m1Btlr )
Allelic Composition: Ank1M1Btlr/Ank1+ (Genetic Background: C57BL/6J-Ank1m1Btlr )
MeSH Terms
  • Anemia, Hemolytic/genetics
  • Animals
  • Ankyrins/chemistry
  • Ankyrins/genetics
  • Ankyrins/metabolism
  • Binding Sites
  • Codon, Terminator
  • Cytoskeleton/metabolism
  • Exons
  • Haploinsufficiency
  • Heterozygote
  • Introns
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Nonsense Mediated mRNA Decay
  • Protein Binding
  • RNA Splicing
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Spherocytosis, Hereditary/genetics
Strain Development
Original mutant was a C57BL/6J G3 ENU-induced mutant; all subsequent crosses to maintain strain were on C57BL/6J background only.
Suggested Control Mice
Wild-type littermates or C57BL/6J mice

MMRRC Genetic QC

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@missouri.edu. Older strains may not have this information.

Research Applications

  • Cell Biology
  • Developmental Biology
  • Hematology
  • Models for Human Disease
    • Spherocytosis, type 1
  • Research Tools

Strain Origin

Donor
Bruce Beutler, M.D., University of Texas Southwestern Medical Center.
Primary Reference
  • Du X, Krieg L, Murray AR, and Beutler B. Record for hema6. MUTAGENETIXtm, B. Beutler and colleagues, The Scripps Research Institute, La Jolla, CA.
  • Huang H, Zhao P, Arimatsu K, Tabeta K, Yamazaki K, Krieg L, Fu E, Zhang T, Du X. A deep intronic mutation in the ankyrin-1 gene causes diminished protein expression resulting in hemolytic anemia in mice. G3 (Bethesda). 2013 Oct 3;3(10):1687-95. (Medline PMID:23934996)

Colony and Husbandry Information

Health Status Report

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@missouri.edu.

Appearance

Coat Color
Black

Breeding

MMRRC Breeding System
Random intra-strain mating
Breeding Scheme(s)
  • Wild-type female x Heterozygous male from the colony or reciprocal mating
  • Homozygous female x Homozygous male from the colony
Overall Breeding Performance
Good

Reproductive Statistics

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
Undetermined
Recommended wean age
3-4 weeks

Order Request Information

Availability Level

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@missouri.edu for more information.

Conditions of Distribution

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.

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

Fees

- Products for this strain are Not Yet Available for Ordering
- If you register interest in this strain, you will be notified when it becomes available for ordering.
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.