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129S6-Gcktm3Mgn

These mice, which contain an activating, A456V mutation within the Gck gene, provide a model for Persistant Hyperinsulinemic Hypoglycemia of Infancy, or PHHI-GK, a rare genetic disease of humans. 

During the generation of this line, male chimeric mice derived by injecting correctly targeted TL1 mESCs into blastocysts from C57Bl/6 animals were mated directly with 129S6 female mice, thereby maintaining the mutation in an inbred state. 

Cryostocks of both 8-cell embryos and sperm from this line exist only at the VUCMR.  

Record History
Added on July 19, 2010 at 10:16 AM by Magnuson, Mark
Modified on July 28, 2017 at 12:56 PM by Magnuson, Mark
Shared with (contributions)
Public: Shared Collection

Mouse Information

Common Name gkA456V
Research Applications Not provided
MMRRC ID Not provided
Jackson Laboratories Stock No Not provided
VUCMR ID DE, DS
Additional Strain Information Not provided

Genetic Alteration

Mutation #1: Targeted Mutagenesis
Type of AlleleGlobal Mutation
Targeted GeneName: Glucokinase
Symbol: Gck
NCBI: 103988
Allele Name: targeted mutation 3
Symbol: Gcktm3Mgn
MGI: 3701764
Description of Targeting Vector

A single base mutation was introduced into exon 10 via site specific mutagenesis to change amino acid 456 from alanine to valine. Genotype by DNA PCR using primers 5'-TGT CTC AAT TTG CTG TGT CCT CCA-3' and 5'-ATG TGT GAG TGT GCC AAT ATG AGT-3'. These primers will amplify a 636 bp fragment from the wild type allele and a 741 bp fragment from the mutant allele. Homozygous mutant mice, which have a phenotype of moderate hypoglycemia, are viable and breed well. Heterozygous animals are mildly hypoglycemic.
Vector Genbank File pBOB2.A456V.gb
Allele Map Not Provided
PCR Genotyping Protocol Not provided
Citations
Publication
Glucokinase thermolability and hepatic regulatory protein binding are essential factors for predicting the blood glucose phenotype of missense mutations. (2007) J Biol Chem 282: 13906-16 (Added 12/10/2013)
PMID: 17353190

Background Strain Information

Strain Type Inbred Strain
Chimera/Founder Genetic Background 129S6/SvEvTac
Current Genetic Background Not provided
Number of Generations Backcrossed Not provided
Strain Description

Need to check how neo cassette was removed.

129SvEv at cryopreservation

Cryopreserved in 2005.

Vial DE - cryopreserved embryos at the 8 cell stage

Vial DS - cryopreserved sperm in vials

Publications / Citations

  1. Glucokinase thermolability and hepatic regulatory protein binding are essential factors for predicting the blood glucose phenotype of missense mutations. Pino MF, Kim KA, Shelton KD, Lindner J, Odili S, Li C, Collins HW, Shiota M, Matschinsky FM, Magnuson MA (2007) J Biol Chem 282(18): 13906-16
    › Primary publication · 17353190 (PubMed) · Added on 12/10/2013

MeSH Terms

Amino Acid Substitution Animals Blood Glucose Carrier Proteins Enzyme Activation Enzyme Stability Glucokinase Glucose Metabolism Disorders Hot Temperature Insulin Liver Mice Mice, Mutant Strains Mice, Transgenic Mutation, Missense Phenotype Protein Binding Recombinant Proteins

Attachments

Document gka456v.neo__wt_protocol.doc - Added on July 27, 2010 at 10:38 AM by Jill Lindner

PCR protocol for genotyping mice

Document K414EA456V_targeting_vector.jpg - Added on July 19, 2010 at 10:16 AM by Mark Magnuson

K414E and A456V targeting vectors