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Strain
B6.129-Gnmttm1Cwa

Summary Data Summary
Official Name B6.129-Gnmttm1Cwa
Common Name B6.129-Gnmttm1Cwa
Description A targeting vector containing a NEO cassette was used to
disrupt exon 1 and promoter region of the gene.

The construct was electroporated into 129/SvJ derived
embryonic stem (ES) cells (IngenKo, Australia). Correctly
targeted ES cells were injected into C57BL/6J blastocysts.
The resulting male chimeric animals were crossed to C57BL/6J
females, and then backcrossed to for 6 generations using a
marker assisted protocol.
Development Status Phenotyping ongoing
Creation Method knockout
Background C57BL/6J
Phenotype Description Glycine N-methyltransferase (GMNT) regulates the ratio of
S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH)
and has a role in methionine metabolism and methylation of
DNA and histones. GNMT is down-regulated in patients with
liver cirrhosis and/or hepatocellular carcinoma. These mice
carry a targeted mutation of the Gnmt gene. Mice that are
homozygous for the targeted mutation are viable, fertile,
normal in size and do not display any gross behavioral
abnormalities. No gene product (protein) is detected by
Western blot or enzyme activity analysis of liver from
homozygous mice. Homozygotes exhibit increased levels of
free methionine and SAM (35 fold) in the liver, and
decreased SAH levels in the liver, with the ratio of SAM/SAH
elevated 100-fold. Serum levels of aminotransferases,
methionine, and SAM are also elevated. Although
heterozygotes have only approximately 50% of wildtype enzyme
activity levels, hepatic methione, SAM and SAH levels are
similar to wildtype control. At 3 months of age, homozygotes
exhibit progressive liver steatosis and fibrosis. At 8
months of age, homozygotes exhibit hypermethlyation of DNA
and develop multifocal hepatocellular carcinoma.
TypeCount
Investigators 1
Genomics - Modifications 1
Experiments 1


Investigators
NameInstitution
David WassermanVanderbilt University


Genomic Information
GeneAllele 1Allele 2Protocol
GnmtknockoutknockoutNot Specified


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