These CMAH knock-out mice may be useful for studying the hydroxylation of sialic acids required for protein/lipid synthesis and pancreatic beta cell function. In combination with other alleles, they may also have applications in studies related to Duchenne muscular dystrophy.
Ajit Varki, University of California, San Diego
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Cmah | cytidine monophospho-N-acetylneuraminic acid hydroxylase |
These Cmah KO mice lack exon 6 of the cytidine monophospho-N-acetylneuraminic acid hydroxylase gene (Cmah or CMP-Neu5Ac hydroxylase). CMAH catalyses the biosynthesis of the sialic acid N-glycolylneuraminic acid (Neu5Gc). Sialic acids (Sias) mediate cell-cell interactions and signaling. They also function as receptors for some pathogens. Humans lack functional CMAH and these mice exhibit a human-like inactivation of CMAH function. KO mice have elevated levels of N-acetylneuraminic acid (Neu5Ac) and sialic acid O acetylation. They exhibit a 65% decrease in pancreatic islet size and area, a 50% decrease in islet number, and a 40% reduction in response to insulin leading to fasting hyperglycemia and glucose intolerance on a high-fat diet. They also display diminished startle response, age-related hearing loss, and a delay in skin wound healing.
When bred to C57BL/10ScSn-Dmdmdx/J mice (Stock No. 001801), lack of CMAH accelerates the onset and severity of Duchenne muscular dystrophy (DMD) seen in the Dmdmdx mice.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these Balb/c-congenic mice could vary from that originally described on a B6J genetic background. We may modify the strain description if necessary as published results become available.
A targeting vector was designed to insert a loxP site upstream of exon 6, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 6 of the cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah) gene. The construct was electroporated into 129/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre-expressing plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 6, intact floxed-neo cassette, or excision of both exon 6 and the neo cassette. Correctly targeted ES cells, lacking both exon 6 and the neo cassette, were injected into blastocysts and resulting chimeric males were bred with C57BL/6N females. Resulting offspring were backcrossed to C57BL/6N mice for at least ten generations, and were brought into The Jackson Laboratory as Stock No. 017588. Subsequently, the donating investigator bred some of these mice to Balb/cAnHsd mice for at least 10 genrations. Upon arrival at The Jackson Laboratory Repository, males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize BALB/cByJ oocytes (Stock No. 001026).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome were segregating, one likely due to the mutation on Chromosome 13.
Allele Name | targeted mutation 1, Ajit Varki |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Cmah- |
Gene Symbol and Name | Cmah, cytidine monophospho-N-acetylneuraminic acid hydroxylase |
Gene Synonym(s) | |
Strain of Origin | 129X1/SvJ |
Chromosome | 13 |
Molecular Note | Exon 6 and a floxed TK/neo were removed via transient cre mediated recombination. |
Mutations Made By | Ajit Varki, University of California, San Diego |
When maintaining a live colony, homozygous mice may be bred together.
When using the C.129X1(B6N)-Cmahtm1Avrk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #028043 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous for Cmah<tm1Avrk> |
Frozen Mouse Embryo | C.129X1(B6N)-Cmah<tm1Avrk>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C.129X1(B6N)-Cmah<tm1Avrk>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C.129X1(B6N)-Cmah<tm1Avrk>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | C.129X1(B6N)-Cmah<tm1Avrk>/J Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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