Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II

Nina Raben, Kanneboyina Nagaraju, Eunice Lee, Paul Kessler, Barry Byrne, Laura Lee, Mary LaMarca, Christina King, Jerrold Ward, Brian Sauer, Paul Plotz

Research output: Contribution to journalArticle

Abstract

We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid ~-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Δ6/Δ6), like the recently published acid α-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M.P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.

Original languageEnglish (US)
Pages (from-to)19086-19092
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number30
DOIs
StatePublished - Jul 24 1998
Externally publishedYes

Fingerprint

Glycogen Storage Disease Type II
Glucosidases
Glycogen
Critical Illness
Genes
Acids
Muscle
Exons
Viverridae
Enzyme activity
Diaphragms
Gene Targeting
Enzymes
Lysosomes
Diaphragm
Gait
Animals
Myocardium
Skeletal Muscle
Phenotype

ASJC Scopus subject areas

  • Biochemistry

Cite this

Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II. / Raben, Nina; Nagaraju, Kanneboyina; Lee, Eunice; Kessler, Paul; Byrne, Barry; Lee, Laura; LaMarca, Mary; King, Christina; Ward, Jerrold; Sauer, Brian; Plotz, Paul.

In: Journal of Biological Chemistry, Vol. 273, No. 30, 24.07.1998, p. 19086-19092.

Research output: Contribution to journalArticle

Raben, Nina ; Nagaraju, Kanneboyina ; Lee, Eunice ; Kessler, Paul ; Byrne, Barry ; Lee, Laura ; LaMarca, Mary ; King, Christina ; Ward, Jerrold ; Sauer, Brian ; Plotz, Paul. / Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 30. pp. 19086-19092.
@article{86fefc819c26450cad5a6f7835af9d6b,
title = "Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II",
abstract = "We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid ~-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Δ6/Δ6), like the recently published acid α-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M.P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.",
author = "Nina Raben and Kanneboyina Nagaraju and Eunice Lee and Paul Kessler and Barry Byrne and Laura Lee and Mary LaMarca and Christina King and Jerrold Ward and Brian Sauer and Paul Plotz",
year = "1998",
month = "7",
day = "24",
doi = "10.1074/jbc.273.30.19086",
language = "English (US)",
volume = "273",
pages = "19086--19092",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

TY - JOUR

T1 - Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II

AU - Raben, Nina

AU - Nagaraju, Kanneboyina

AU - Lee, Eunice

AU - Kessler, Paul

AU - Byrne, Barry

AU - Lee, Laura

AU - LaMarca, Mary

AU - King, Christina

AU - Ward, Jerrold

AU - Sauer, Brian

AU - Plotz, Paul

PY - 1998/7/24

Y1 - 1998/7/24

N2 - We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid ~-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Δ6/Δ6), like the recently published acid α-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M.P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.

AB - We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid ~-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Δ6/Δ6), like the recently published acid α-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M.P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.

UR - http://www.scopus.com/inward/record.url?scp=14444274334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14444274334&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.30.19086

DO - 10.1074/jbc.273.30.19086

M3 - Article

C2 - 9668092

AN - SCOPUS:14444274334

VL - 273

SP - 19086

EP - 19092

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 30

ER -