AMPK Methods and Protocols

Table 2
(continued)

Model and

PRKAG2

mutation Main observations

Measured effect on

AMPK activity Reference

cardiac glycogen accumulation (80-fold and

15-fold greater than non-TG and TGWT,

respectively). Overt ventricular pre-excitation.

Marked ventricular dilatation and severely

impaired function (EF¼26% versus 58% in

non-TG). Increased spontaneous mortality,

more prominent in males

TGT400N

(Thr400Asn)

TGWTcontrol not employed

TGT400N—cardiac hypertrophy apparent by

1 week of age (~4-fold increased HW:BWover

non-TG by age 4 weeks). Marked myocyte

vacuolization and glycogen retention (~100-

fold greater than WT at 4 weeks). Later

emergence of ventricular remodelling with

dilatation and dysfunction (8–12 weeks).

Partial phenotypic rescue of TGT400Nby

crossbreeding with TGα2DN

Initial increase in AMPK

activity from 2 days to

2 weeks followed by

decreased below

TGWTlevels

[35]

N485I and

R528G

knock-in

(KI) lines

(Asn488I and

Arg531Gly)

No significant differences in cardiac expression

ofγ2-AMPK orα1-/α2-subunit mRNA

expression between WT and knock-in mice

KI—small but significant increase in absolute

cardiac mass in both lines at age 24 weeks.

Increased cardiac glycogen in R528G KI only

at age 26 weeks. Increased sinus cycle length in

both KI lines. Significant small reduction in

PR interval in R528G KI (13%) with no

discernible differences in QRS duration from

WT controls

Elevated pACC in cardiac

and skeletal muscle in

KI lines

[31]

Fig. 3Ventricular pre-excitation in transgenic mice overexpressing mutantPRKAG2. Surface ECG recordings
of TGWT(left) and TGR302Q(right) mice, illustrating a shortened PR interval and widened QRS complex in
TGR302Qmice consistent with ventricular pre-excitation (Reproduced from ref.33 with permission from
Wolters Kluwer Health, Inc.)

PRKAG2 syndrome 591