Gaa KO Mice

Catalog Number: C001702

Strain Name: C57BL/6JCya-Gaaem1/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The GAA gene encodes lysosomal acid alpha-glucosidase, a critical enzyme responsible for the hydrolysis of glycogen within lysosomes. Expressed across various tissues, including muscle and liver, GAA resides on mouse chromosome 11 and human chromosome 17 and follows an autosomal recessive inheritance pattern [1]. Pathogenic mutations in GAA lead to Glycogen Storage Disease Type II, commonly known as Pompe disease, a condition characterized by the intralysosomal accumulation of glycogen [2]. This accumulation primarily affects cardiac and skeletal muscle, resulting in progressive muscle weakness. In severe infantile-onset cases, Pompe disease manifests with marked cardiomyopathy and respiratory insufficiency [2-3]. Animal models deficient in Gaa have proven invaluable for elucidating disease mechanisms and evaluating therapeutic interventions.

The Gaa KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Gaa gene (the homolog of the human GAA gene) in mice. This model is used to research the pathogenic mechanisms of Glycogen Storage Disease Type II (Pompe disease) and develop related therapeutic strategies.

 

Strain Strategy

The mouse Gaa gene in mice consists of 20 exons, with the start codon in exon 2 and the stop codon in exon 20. This strain was created by gene-editing techniques that knocked out the region spanning exons 3 ~ 15.


Application

  • Studies of lysosomal glycogen metabolism;
  • Research on Glycogen Storage Disease Type II (Pompe disease) pathogenesis and therapeutic drug evaluation;

 

Validation data

1. Grip Strength


Figure 1. Grip strength testing of 12-week-old homozygous female Gaa KO mice and wild-type (WT) mice (n=5). The results show that the grip strength values for the Gaa KO mice were lower compared to WT, consistent with the expected phenotype.

 

2. Body Weight


Figure 2. Body weight of 12-week-old homozygous female Gaa KO mice and wild-type (WT) mice (n=5). The results show that the body weight of the Gaa KO mice was significantly higher than that of the WT mice, consistent with the expected phenotype.

 

3. Glycogen Content Detection


Figure 3. Glycogen content detection of the heart and gastrocnemius muscle in 12-week-old homozygous female Gaa KO mice and wild-type (WT) mice (n=3). The results show that the glycogen content in the heart and gastrocnemius muscle of the Gaa KO mice is significantly higher than that of the wild-type control group, and the phenotype is consistent with expectations. Specifically, the glycogen content in the heart of the Gaa KO mice is about 33 times higher than that of the wild-type, while in the gastrocnemius muscle it is about 2 times higher.

4. GAA Activity Detection


Figure 4. GAA activity detection of the heart (Heart) and gastrocnemius muscle (Gastrocnemius; GA) in 12-week-old homozygous female Gaa KO mice and wild-type (WT) mice (n=3). The results show that the GAA activity in the heart and gastrocnemius muscle of the Gaa KO mice is significantly lower than that of the wild-type control group, and the phenotype is consistent with expectations. Specifically, the GAA activity in the heart and gastrocnemius muscle of the Gaa KO mice is about 10 times lower than that of the wild-type.

 

References
[1]Taverna S, Cammarata G, Colomba P, Sciarrino S, Zizzo C, Francofonte D, Zora M, Scalia S, Brando C, Curto AL, Marsana EM, Olivieri R, Vitale S, Duro G. Pompe disease: pathogenesis, molecular genetics and diagnosis. Aging (Albany NY). 2020 Aug 3;12(15):15856-15874.
[2]Unnisa Z, Yoon JK, Schindler JW, Mason C, van Til NP. Gene Therapy Developments for Pompe Disease. Biomedicines. 2022 Jan 28;10(2):302.
[3]Labella B, Cotti Piccinelli S, Risi B, Caria F, Damioli S, Bertella E, Poli L, Padovani A, Filosto M. A Comprehensive Update on Late-Onset Pompe Disease. Biomolecules. 2023 Aug 22;13(9):1279.