. Author manuscript; available in PMC: 2016 Sep 18.

Published in final edited form as: J Mol Endocrinol. 2016 Mar 3;56(4):T157–T174. doi: 10.1530/JME-16-0014

Table 1.

Mouse models used to study α-MSH signaling in obesity.

Yellow lethal (A^y) and related alleles (A^iy, A^sy, A^vy, A^iapy)	Spontaneous mutation resulting in agouti (Asip) ectopic expression, homozygous lethal; unrelated to agouti ectopic expression, moderate hyperphagia, hyperinsulinemia (2–5 × normal), late-onset hyperglycemia, lean body mass, ↓ energy expenditure, ↑ sensitivity to stressors, milder obesity syndrome than ob/ob or db/db, yellow fur color	Dickie (1962, 1969), Frigeri et al. (1983), Bultman et al. (1992), Michaud et al. (1993, 1994a,b),Miller et al. (1993), Klebig et al. (1995)
AgRP transgene	Expression of the AgRP under the control of α-actin promoter, same metabolic phenotype as A^vy, same fur color as wildtype littermates	Graham et al. (1997)
AgRP^DTR/DTR	Cross of mice harboring a loxP flanked diphtheria toxin receptor with animals with Cre recombinase under control of AgRP promoter Ablation of AgRP/NPY neurons of the arcuate nucleus of the hypothalamus, ↓↓ food intake, ↓ body weight, complete ablation results in starvation and death	Gropp et al. (2005), Luquet et al. (2005), Wu et al. (2008a,b)
POMC^−/−	Hyperphagic, ↓ energy expenditure, adrenal insufficiency, develop obesity exacerbated with high-fat diet, lighter than littermates-colored dorsal and yellow ventral fur	Yaswen et al. (1999), Challis et al. (2004)
POMC, AgRP^−/−	Hyperphagic, ↓ energy expenditure, α-MSH but not AgRP administration rescues wildtype phenotype, lighter than littermates-colored dorsal and yellow ventral fur similar to POMC^−/−	Corander et al. (2011)
MC4R^−/−	Hyperphagic, less obese than ob/ob or db/db, early onset obesity (5–7 weeks), ↓ energy expenditure, dosage effect with, +/− animals have intermediate phenotype, increased linear growth, same fur color as wildtype littermates	Huszar et al. (1997)
Targeted deletion of MC4R at the PVH	Vglut2-ires-Cre;Mc4r^lox/lox, targeted deletion of MC4R in glutamatergic neurons: same phenotype as MC4R null mice including ↑ hyperphagia, ↑ body weight, and ↑ linear growth Sim1-Cre;Mc4r^lox/lox: targeted deletion of MC4R in single-minded 1 positive (SIM1⁺) neurons: intermediate phenotype between MC4R^−/− and Mc4r^lox/lox control mice	Balthasar et al. (2004), Shah et al. (2014)
MC3R^−/−	Moderate obesity syndrome of late onset (26 weeks), ↑ body weight predominant in females, ↑ adiposity, ↑ energy efficiency, no change in lean mass, no change in linear growth, same fur color as wildtype littermates	Butler et al. (2000), Chen et al. (2000), Sutton et al. (2006)
MC3R, MC4R^−/−	Augmented obesity syndrome compared with MC4R^−/− or MC3R^−/−; including ↓ energy expenditure, no change in food ingestion after MTII administration, same fur color as wildtype littermates	Chen et al. (2000)
Mahogany (Atrn^mg) and related alleles (Atrn^mg-3j, Atrn^mg-L)	Autosomal recessive mutation reverting the phenotype of A^y including obesity albeit hyperphagia is present, Atrn encodes for attractin, a melanocortin receptor coreceptor.Atrn^mg is a defective splice variant allele that results from a 5 kb retroviral insertion in introns 26 and 27 Fur color reflects eumelanin predominance with diminished pheomelanin, darkened ears, and tail (umbrous coat). Atm^mg-3j; a null allele of Atrn, has darker fur	Lane & Green (1960), Dinulescu et al. (1998), Gunn et al. (1999)
Mahogunin, ring finger 1 (Mgrn1^md)	Mgrn1 encodes an E3 ubiquitin ligaseThe Mgrn1^md allele displays a similar phenotype to Atrn^mg and related alleles	Dinulescu et al. (1998), Phan et al. (2002)
Mrap2^−/−	Melanocortin receptor accessory protein 2 (MRAP2) knockoutLate-onset ↑ hyperphagia, early onset ↑ body weight, ↑ white fat tissue depots ↓ lean mass, same fur color as wildtype littermates	Asai et al. (2013)