JF1/B6F1 Ngly1−/− mouse as an isogenic animal model of NGLY1 deficiency

N-Glycanase 1 (NGLY1) deficiency is a congenital disorder caused by mutations in the NGLY1 gene. Because systemic Ngly1−/− mice with a C57BL/6 (B6) background are embryonically lethal, studies on the mechanism of NGLY1 deficiency using mice have been problematic. In this study, B6-Ngly1−/+ mice were...

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Bibliographic Details
Published in:Proceedings of the Japan Academy, Series B Series B, 2021/02/10, Vol.97(2), pp.89-102
Main Authors: ASAHINA, Makoto, FUJINAWA, Reiko, FUJIHIRA, Haruhiko, MASAHARA-NEGISHI, Yuki, ANDOU, Tomohiro, TOZAWA, Ryuichi, SUZUKI, Tadashi
Format: Article
Language:English
Subjects:
animal model
Animal models
Animals
aspartylglycosamine
Biomarkers
Congenital anomalies
Congenital diseases
Congenital Disorders of Glycosylation - genetics
congenital neurological disorder
CRISPR
Disease Models, Animal
Genomes
Glycoproteins
Laboratory animals
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
motor dysfunction
Mutation
N-glycanase
neuroinflammation
NGLY1 deficiency
Original
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase - deficiency
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase - genetics
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase - metabolism
Rodents
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Summary:N-Glycanase 1 (NGLY1) deficiency is a congenital disorder caused by mutations in the NGLY1 gene. Because systemic Ngly1−/− mice with a C57BL/6 (B6) background are embryonically lethal, studies on the mechanism of NGLY1 deficiency using mice have been problematic. In this study, B6-Ngly1−/+ mice were crossed with Japanese wild mice-originated Japanese fancy mouse 1 (JF1) mice to produce viable F2 Ngly1−/− mice from (JF1×B6)F1 Ngly1−/+ mice. Systemic Ngly1−/− mice with a JF1 mouse background were also embryonically lethal. Hybrid F1 Ngly1−/− (JF1/B6F1) mice, however, showed developmental delay and motor dysfunction, similar to that in human patients. JF1/B6F1 Ngly1−/− mice showed increased levels of plasma and urinary aspartylglycosamine, a potential biomarker for NGLY1 deficiency. JF1/B6F1 Ngly1−/− mice are a useful isogenic animal model for the preclinical testing of therapeutic options and understanding the precise pathogenic mechanisms responsible for NGLY1 deficiency.
ISSN:0386-2208
1349-2896
1349-2896
DOI:10.2183/pjab.97.005