. 2019 Mar 14;13:344–358. doi: 10.1016/j.omtm.2019.03.001

Table 1.

Interventional Trials in Mouse Models of PWS

Strain	Treatment	Treatment Administration	Note	Outcome	Group Size (M/F)	Age	Reference	Title
Magel2^tm1.1Mus	oxytocin	i.p. single injection, 2 μg	^a	survival	n = 33–51, M and F	3–5 h	⁵	A single postnatal injection of oxytocin rescues the lethal feeding behavior in mouse newborns deficient for the imprinted Magel2 gene
Magel2^tm1.1Mus	oxytocin	i.p. daily, 7 days, 2 μg	^b	survival, social behavior	n = 12–14, M	0–6 d, test adult	²⁹	An early postnatal oxytocin treatment prevents social and learning deficits in adult mice deficient for Magel2, a gene involved in PWS and autism
Magel2^tm1.1Mus	oxytocin	i.p. single injection, 2 μg	^c	social recognition deficits	n = 12–14, M	adult	²⁹	An early postnatal oxytocin treatment prevents social and learning deficits in adult mice deficient for Magel2, a gene involved in PWS and autism
Magel2^tm1Stw	MT-II	i.p. single injection, 2.5 mg/kg	^d	24 h food intake	n = 6, M	3–4 months	⁶	Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice
Magel2^tm1Stw	setmelanotide	i.p. single injection (0.04, 0.1, 0.2 or 1 mg/kg)	^e	food intake, EE, RER	n = 6, M	2–3 months	³⁴	Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist
Magel2^tm1Stw	sleeve gastrectomy	surgery	^f	weight, food intake, fat/lean mass, fasting glucose, glucose tolerance, counter-regulation	n = 7–12, M	5–7 months, HFD	³⁵	Sleeve gastrectomy leads to weight loss in the Magel2 knockout mouse
Magel2^tm1Stw	JD5037 or SLV319	i.p. daily 28 d, 3 mg/kg	^g	weight, food intake, body comp, activity, metabolism	n = 5–10, M and F	3–4 months, HFD or STD	³⁶	Targeting the endocannabinoid and CB1 receptor system for treating obesity in PWS
Magel2^tm1Stw	OEA	i.p. single injection,10 mg/kg	^h	24 h food intake	n = 14–15, M	adult	³⁹	Dysfunctional oleoylethanolamide signaling in a mouse model of PWS
Magel2^tm1Stw	diazoxide	ground into food, 150 mg/kg/day, 6 weeks	ⁱ	weight, body composition, activity, fasting glucose	n = 6, M and F	5–7 months, HFD	³⁸	Chronic diazoxide treatment decreases fat mass and improves endurance capacity in an obese mouse model of PWS
Magel2^tm1Stw	oleoyl a-methyl serine (HU-671)	once daily, 0.5 mg/kg, 6 weeks	^j	structural analysis of the trabecular and cortical bones	n = 4–11, F	6–12 weeks	³⁷	Magel2 modulates bone remodeling and mass in Prader-Willi syndrome by affecting oleoyl serine levels and activity
Ndn^tm1.1Mus	fluoxetine	10 mg/kg/day from P5–P15	^k	plethysmography (% with apnea, apnea/h, apnea duration)	n = 8, M and F	5–15 d, measure 0, 15, 45 days later	⁷¹	Necdin shapes serotonergic development and SERT activity modulating breathing in a mouse model for PWS
Snord116^tm1.1Uta	[D-Lys3]-GHRP6	i.p. daily, 12 μmol/kg, 6 days	^l	food intake	n = 7–9, M	6–12 months	¹¹³	Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for PWS
Snord116^tm1.1Uta	SPA	i.p. daily, 4.5 μmol/kg, 6 days	^m	food intake	n = 8, M	6–12 months	¹¹³	Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for PWS
Snord116^tm1.1Uta	YIL-781	i.p. daily, 134 μmol/kg, 6 days	ⁿ	food intake	n = 9–10, M	6–12 months	¹¹³	Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for PWS
Snord116^tm1.1Uta	exenatide	i.p. twice daily, 24 μg/kg, 17 days	^o	food intake	n = 7–9, M	6–12 months	¹¹³	Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for PWS
Snord116^tm1.1Uta	GHSR agonist HM01	s.c. daily, 30 μg/g, 14 days	^p	body weight, length, mortality	n = 9–17, M and F	1–14 days	¹¹⁴	Ghrelin receptor agonist rescues excess neonatal mortality in a Prader-Willi syndrome mouse model
Snord116^tm1.1Uta	Carraluma fimbriata extract	orally in gel, 33 or 100 mg/kg/day, 10 weeks	^q	food intake after stimulation	n = 6, M and F	4–15 weeks	¹⁶⁵	Caralluma fimbriata extract activity involves the 5-HT2c receptor in PWS Snord116 deletion mouse model
Snord116^tm1.1Uta	thermoneutral (30°C)	16 weeks	^r	body weight, body comp, length, BMD, energy intake	n = 9–14, M	from 4 to 20 weeks	¹⁰⁶	Ambient temperature modulates the effects of the PWS candidate gene Snord116 on energy homeostasis
Snrpn^tm2Cbr (PWS-ICdel)	thermoneutral (30°C)	9 weeks	^s	food intake, fat mass, weight gain	n = 5–6, M and F	6–15 months	¹¹⁸	Paradoxical leanness in the imprinting-center deletion mouse model for PWS
Snrpn^tm2Cbr (PWS-ICdel)	WAY-161503	s.c. single injection, 3 mg/kg or 10 mg/kg	^t	postfast refeeding	n = 12–14, M and F	adult	¹²²	Increased alternate splicing of Htr2c in a mouse model for Prader-Willi syndrome leads disruption of 5HT2C receptor mediated appetite
Del(7Ube3a-Snrpn)1Alb	UNC0642	i.p. daily P7–P12, 2.5 mg/kg	^u	% survival, body weight	n = 6–27, M and F	7–90 days	¹²³	Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of PWS

i.p., intraperitoneal; s.c., subcutaneous; EE, energy expenditure; RER, respiratory exchange ratio; HFD, high-fat diet; SD, standard diet; BMD, bone mineral density; P, postnatal day.

Rescued the death rate of Magel2 mice with a single injection of oxytocin 3–5 h after birth.

Daily oxyocin injections in the first 7 postnatal days increased survival and prevented social and learning deficits in Magel2 adult male mice.

Reversed social recognition deficits in Magel2 mice despite a temporary sedative effect.

Reduced food intake in Magel2 mice, compared to vehicle. This effect was still evident 24 h after injection. Lesser extent of reduced food intake for the first 2 h of refeeding in control mice. This effect was no longer present by 4 h.

Reduced food intake, increased energy expenditure, and increased activity in WT and Magel2 mice compared to vehicle. Magel2 mice responded at lower dosages of setmelanotide.

Similar weight loss in both Magel2 and WT mice by specifically causing loss of fat but not lean mass. Lowered fasting glucose and improved glucose tolerance in both WT and Magel2 mice.

Reversed obesity, reduced hyperphagia, increased total energy expenditure and voluntary activity, food intake and carbohydrate intake, and improved metabolic outcomes in obese Magel2 mice.

Reduced food intake in Magel2 mice, compared to vehicle. Effect attributed to decreased meal size and accompanying increase in satiety ratio (postmeal interval/meal size).

ⁱ

Decreased fat mass, increased percent lean mass, and eliminated hyperglycemia in male and female diet-induced obese mice. Both WT and Magel2 had improved endurance.

Restored bone density and bone mass, decreased bone resorption, and increased bone formation.

Daily fluoxetine treatment of Ndn pups from P5–P15 suppressed their respiratory deficits.

No suppression of food intake in WT or Snord116 mice.

ⁿ

Reduced food intake only on day 1 in WT and Snord116 mice.

Food intakes for WT and Snord116 mice were reduced to ∼84%.

GHSR, growth hormone secretagogue receptor. Reduced body weight and length in male Snord116 pups, reduced mortality in Snord116 pups.

Differences between strains in 4-h food intake after stimulation of appetite with agents. Sexes not separately analyzed.

Normalized low BMD and BMC, high energy expenditure and low physical activity, but not low body weight, in Snord116 mice.

Increased BAT mass in WT and ICdel males but failed to induce a corresponding elevation in WAT mass. Proportionate hyperphagia in ICdel males abolished at thermoneutrality.

Reduced food consumption in WT but not PWS-ICdel mice compared to vehicle.

Improved survival and increased growth of Del(7Ube3a-Snrpn)1Alb neonatal mice, 2/60 survived to P90.