The Ngly1R539X allele has a 1 bp replacement in the mouse N-glycanase 1 gene that encodes a nonsense mutation, resulting in a premature stop codon. This mutation corresponds to the R542X mutation identified in the patient population as a disease causing variant in Congenital Disorders of Glycosylation Type 1v.
Cathleen Lutz, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Endonuclease-mediated (Humanized sequence) | Ngly1 | N-glycanase 1 |
The Ngly1R539X allele has a 1 bp replacement (CGA-to-TGA) in the mouse N-glycanase 1 gene that encodes an R539X nonsense mutation, resulting in a premature stop codon. This mutation corresponds to the R542X mutation in human patients identified as a disease causing variant in Congenital Disorders of Glycosylation Type 1v; an autosomal recessive multi-system disorder characterized by global developmental delay, hypotonia, abnormal involuntary movements and poor tear production. N-glycanase 1 is an enzyme that catalyzes the deglycosylation of misfolded N-linked glycoproteins so that they can be processed properly. Mice heterozygous for the Ngly1R539X allele are viable and fertile. Homozygous mice are lethal. The donating investigator reports homozygotes are present in Mendelian ratios to embryonic day (E)18, and ~20% of the expected homozygotes are born but die within 1-2 days.
To date (September 2015), full characterization is in progress. As the mice are characterized, we will modify the strain description.
This mouse model is available by way of a collaborative effort between the Grace Wilsey Foundation and The Jackson Laboratory.
The Ngly1R539X allele was created by Dr. Cathleen Lutz (The Jackson Laboratory) using CRISPR/cas9 endonuclease-mediated genome editing in C57BL/6J mouse zygotes (Stock No. 000664).
Specifically, the N-glycanase 1 locus (Ngly1) on chromosome 14 was targeted with single guide RNAs designed to create a C-to-T nucleotide replacement (CGA-to-TGA) encoding an arginine 539-to-termination codon nonsense mutation (R539X).
The sgRNAs and Cas9 endonuclease were introduced into C57BL/6J-derived fertilized eggs by pronuclear injection. Embryos were transferred to pseudopregnant females, and correctly targeted pups (identified by sequencing and PCR) were bred to C57BL/6J inbred mice for germline transmission. Mice from founder 93 were further bred to C57BL/6J inbred mice to develop the colony.
Allele Name | endonuclease-mediated mutation 10, Cathy Lutz |
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Allele Type | Endonuclease-mediated (Humanized sequence) |
Allele Synonym(s) | Ngly1R539X |
Gene Symbol and Name | Ngly1, N-glycanase 1 |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 14 |
Molecular Note | Using CRISPR/cas9 endonuclease mediated genome editing, single guide RNAs are designed to create a C-to-T nucleotide replacement (CGA-to-TGA) encoding an arginine 539-to-termination codon nonsense mutation (R539X). This mutation corresponds to the R542X mutation identified in the patient population as a disease causing variant in Congenital Disorders of Glycosylation Type 1v. |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype littermates, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice are lethal. The donating investigator reports homozygotes are present in Mendelian ratios to embryonic day (E)18, and ~20% of the expected homozygotes are born but die within 1-2 days.
When using the Ngly1R539X mouse strain in a publication, please cite the originating article(s) and include JAX stock #028221 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Ngly1<em10(R539X)Lutzy> |
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