C57BL/6J-Ngly1^em9Lutzy/J

Stock number: 027962
Product name: Ngly1^R399del
Strain synonyms: C57BL/6J-Ngly1<em9(R399del)Lutzy>/J
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

The Ngly1^R399del allele has a 3 nucleotide in-frame deletion in the mouse N-glycanase 1 gene that corresponds to a single amino acid deletion (R402del) in the human protein. This mutation has been identified as a disease causing variant in Congenital Disorders of Glycosylation Type 1v.

Detailed description

The Ngly1^R399del allele has a 3 nucleotide in-frame deletion in the mouse N-glycanase 1 gene that corresponds to a single amino acid deletion (R402del) in the human protein. This mutation has been 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 Ngly1^R399del 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 to include expression of a truncated RNA/protein, as well as further patholgical assessments.

This mouse model is available by way of a collaborative effort between the Grace Wilsey Foundation and The Jackson Laboratory.

Development

The Ngly1^R399del 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 delete the 3 nucleotides encoding arginine 399 (synonymous to the human R402del mutation). 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 153 were further bred to C57BL/6J inbred mice to develop the colony.

Allele

Symbol: Ngly1^em9Lutzy
Name: endonuclease-mediated mutation 9, Cathy Lutz
MGI accession ID: MGI:5752816
Generation method: Endonuclease-mediated
Attributes: Not Applicable
Synonyms: Ngly1^R399del
Marker symbol: Ngly1
Marker name: N-glycanase 1
Marker synonyms: 1110002C09Rik; CDDG; CDG1V; Png1; PNG-1; PNGase
Chromosome: 14
Strain of origin: C57BL/6J
Molecular note: Using CRISPR/cas9 endonuclease mediated genome editing, single guide RNAs are designed to delete the 3 nucleotides encoding arginine 399 (synonymous to the human R402del mutation).