Phenotypes associated with this allele

• Allele Symbol: Gaa^tm1Vdp
• Allele Name: targeted mutation 1, Ans T van der Ploeg
• Allele ID: MGI:2179961
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gaa^tm1Vdp/Gaa^tm1Vdp	B6.129P2-Gaa^tm1Vdp	MGI:3619141
hm2	Gaa^tm1Vdp/Gaa^tm1Vdp	either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * FVB)	MGI:3619140

Genotype
MGI:3619141

hm1

• Allelic Composition: Gaa^tm1Vdp/Gaa^tm1Vdp
• Genetic Background: B6.129P2-Gaa^tm1Vdp

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

muscle

decreased skeletal muscle mass ( J:105167 )

• unlike wild-type mice, homozygotes show an age-dependent decrease in (dorsiflexor) muscle mass, with an 11% and 24% mass reduction noted at 13 and 20 months, respectively

muscular atrophy ( J:105167 )

• one-third of the decline in muscle performance is attributed to muscle atrophy

• the remaining two/thirds are attributed to reduced muscle quality i.e. a reduction in mechanical performance per unit muscle mass

• no decline in protein content per unit muscle mass is observed

abnormal muscle physiology ( J:105167 )

progressive muscle weakness ( J:105167 )

• mutant dorsiflexor muscles exhibit a normal isometric torque at 7 months, but show a ~50% reduction between 7 and 13 months, with no further changes thereafter

• mutant dorsiflexor muscles display a 29%, 53%, and 68% reduction in peak power at 7, 13, and 20 months, respectively, with no further changes thereafter

• the mutant dorsiflexor complex displays a 25% reduction in optimal shortening angular velocity at 7, 13, and 20 months

• mutant muscles show no significant differences in the rise or the half-relaxation time of the isometric torque, suggesting normal calcium handling

growth/size/body

increased body mass index ( J:105167 )

• at 20 months, wild-type mice show a significant increase in body mass; in contrast, age-matched mutant mice can be either obese or lean

Genotype
MGI:3619140

hm2

• Allelic Composition: Gaa^tm1Vdp/Gaa^tm1Vdp
• Genetic Background: either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * FVB)

cardiovascular system

abnormal heart morphology ( J:45386 )

• at 32 weeks, homozygotes exhibit a round, swollen and pale heart relative to the smaller, oval and darker stained heart of wild-type mice

abnormal myocardial fiber morphology ( J:45386 )

• at 13 weeks, homozygotes display large glycogen-containing lysosomes in heart muscle fibers

globular heart ( J:45386 )

• at 32 weeks of age, the heart is round rather than oval

enlarged heart ( J:45386 )

• at 32 weeks, homozygotes display cardiac enlargement

heart left ventricle hypertrophy ( J:45386 )

heart right ventricle hypertrophy ( J:45386 )

dilated heart left ventricle ( J:45386 )

dilated heart right ventricle ( J:45386 )

abnormal impulse conducting system conduction ( J:45386 )

abnormal QRS complex ( J:45386 )

• at 32 weeks, several homozygotes display an abnormal electrocardiogram with a high voltage QRS complex

cardiomyopathy ( J:45386 )

• at 9 months, homozygotes are viable and fertile but exhibit signs of a developing cardiomyopathy in the absence of overt clinical symptoms

growth/size/body

enlarged heart ( J:45386 )

• at 32 weeks, homozygotes display cardiac enlargement

heart left ventricle hypertrophy ( J:45386 )

heart right ventricle hypertrophy ( J:45386 )

homeostasis/metabolism

abnormal glycogen homeostasis ( J:45386 )

• at P8, homozygotes display generalized and progressive glycogen storage, with glycogen-containing lysosomes detected in liver, heart and skeletal muscle cells, smooth muscle cells of blood vessels, Schwann cells, and anterior horn cells

muscle

abnormal myocardial fiber morphology ( J:45386 )

• at 13 weeks, homozygotes display large glycogen-containing lysosomes in heart muscle fibers

heart left ventricle hypertrophy ( J:45386 )

heart right ventricle hypertrophy ( J:45386 )

cardiomyopathy ( J:45386 )

• at 9 months, homozygotes are viable and fertile but exhibit signs of a developing cardiomyopathy in the absence of overt clinical symptoms

abnormal skeletal muscle fiber morphology ( J:45386 )

• at 6 weeks, homozygotes display large glycogen-containing lysosomes in between and parallel to the fibrils of the femoral and sural muscles, triceps and skeletal muscle of the tongue; more numerous focal deposits of glycogen are detected by 13 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
glycogen storage disease II		DOID:2752	OMIM:232300	J:45386