AMPK Methods and Protocols

Table 2
Murine models of PRKAG2 cardiomyopathy

Model and

PRKAG2

mutation Main observations

Measured effect on

AMPK activity Reference

TGN488I

(Asn488Ile)

Both TGWTand TGN488I—20-fold greater

cardiacPRKAG2RNA andγ2-protein

expression than non-TG mice

TGWT—cardiac hypertrophy (1.5-fold increased

HW:BW over non-TG) and cardiac glycogen

accumulation (sixfold increased glycogen:HW

over non-TG). No decline in cardiac function

by 20 weeks

TGN488I—severe cardiac hypertrophy (2.4-fold

increased HW:BW over non-TG) and

profound cardiac glycogen accumulation

(33-fold increased glycogen:HW over

non-TG). Overt pre-excitation (short PR/δ

wave) in ~50% with EP study evidence of

accessory AV connections. Thinning and

disruption of the annulus fibrosus with

multiple vacuolated, glycogen-loaded

myocytes. Cardiac conduction system disease.

Severe LV dysfunction by 20 weeks on echo.

Stress-induced syncope and sudden death

(20–40 weeks)

Elevated cardiac basalα1-

andα2-associated

AMPK activity in

TGN488Iversus TGWT

[32, 37]

TGR302Q

(Arg302Gln)

TGWT—cardiac hypertrophy (HW 140 mg vs

non-TG 117 mg)

TGR302Q—severe cardiac hypertrophy (~3-fold

increased HW over non-TG). Twofold

increased expression of B-type natriuretic

peptide over TGWTand non-TG.

Cardiomyocyte vacuolation and glycogen

retention. Muscle bundles extending from the

atrium to the ventricle in the region of the

fibrous body. Ventricular dilatation and

reduced systolic function on echo. Overt

ventricular pre-excitation on surface ECG.

Increased sinus cycle length and functioning

procainamide-sensitive accessory pathways.

Inducible orthodromic atrioventricular

reentrant tachycardia with atrial programmed

electrical stimulation

Reduced cardiacγ2-

specific and total

AMPK activity in adult

TGR302Qversus

non-TG. No

significant response of

TGR302Qto AMP

Increased cardiac AMPK

activity in neonatal

(7-day-old) TGR302Q

versus non-TG

[33, 49]

TGR531G

(Arg531Gly)

TGWT—cardiac hypertrophy (1.3-fold increased

LV mass over non-TG), significant from

4 weeks. Fivefold increased cardiac glycogen

content over non-TG at 8 weeks. Normal

ventricular volumes and function

TGR531G—severe cardiac hypertrophy (2.5-fold

increased LV mass over non-TG). Profound

Cardiacγ2-associated

AMPK activity near-

undetectable in 4- and

8-week-old TGR531G

mice but comparable

to non-TG at 1 week

of age

[34]

(continued)

590 Arash Yavari et al.