JAX Mouse Strain Datasheet - 006414

B6;129S4-Mc4r^tm1Lowl/J

Stock No:: 006414 |; loxTB Mc4r

Targeted Mutation

Repository Live

Overview

Also Known As: loxTB Mc4r

Homozygous mice exhibit severe early-onset obesity, accompanied by hyperphagia, increased snout-anus length and hyperinsulinemia. The function of this disrupted allele can be restored by the enzymatic activity of Cre-recombinase. These mutant mice may be useful in studies of neurobiology, obesity, diabetes, hunger/appetite, and fat and energy metabolism.

Donating Investigator

Bradford B. Lowell, Beth Israel Deaconess Med Cntr (Harvard)

Genetic overview

Genetic Background	Generation
	?+N1pN1F17 (19-SEP-16)

Mc4r^tm1Lowl

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Null/Knockout)	Mc4r	melanocortin 4 receptor

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Research Applications

Diabetes and Obesity Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$263.00 Domestic price for female

$526.00 Domestic price for breeder pair

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Details

Detailed Description

The mice have a loxp-flanked transcriptional blocking (loxTB) sequence that prevents normal endogenous gene transcription and translation from the endogenous locus. As such, homozygous mice are devoid of functional mRNA in all tested regions of the brain. Homozygous mice exhibit severe early-onset obesity, accompanied by hyperphagia, increased snout-anus length and hyperinsulinemia. The function of this disrupted allele can be restored by the enzymatic activity of Cre-recombinase. These mutant mice may be useful in studies of neurobiology, obesity, diabetes, hunger/appetite, and fat and energy metabolism.

When bred to a strain expressing Cre recombinase in the hypothalamus see Stock No. 006395 for example), this mutant mouse strain exhibits as intermediate phenotype in comparison to homozygous null mice.

When crossed to STOCK Slc32a1^tm2(cre)Lowl/J (see Stock No. 016962) Cre recombinase expression in inhibitory GABAergic neuron cell bodies results in offspring that exhibit obesity.

When crossed to B6;129S-Oxt^{tm1.1(cre)Dolsn}/J (see Stock No. 024234) Cre recombinase expression in oxytocin-expressing cells results in offspring that exhibit obesity.

Development

A targeting vector was designed to insert a loxp-flanked transcriptional blocker sequence (loxTB) between the transcriptional start site and ATG of the endogenous gene. The blocker sequence contains an SV40 enhancer, neomycin resistance gene, two HSV-TK polyA sequences, and an additional transcriptional pause signal from the pGL3-control vector. The construct was electroporated into 129S4/SvJae-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Chimeric mice were bred to C57BL/6 mice. Mutant mice heterozygous for the "loxTB Mc4r" allele were bred together and maintained as such prior to arrival at The Jackson Laboratory.

Control Suggestions

Wild-type from the colony

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Balthasar N; Dalgaard LT; Lee CE; Yu J; Funahashi H; Williams T; Ferreira M; Tang V; McGovern RA; Kenny CD; Christiansen LM; Edelstein E; Choi B; Boss O; Aschkenasi C; Zhang CY; Mountjoy K; Kishi T; Elmquist JK; Lowell BB. 2005. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123(3):493-505. PubMed: 16269339 MGI: J:115192

View All References

Genetics

Mc4r^tm1Lowl

Allele Symbol: Mc4r^tm1Lowl

Allele Name	targeted mutation 1, Bradford B Lowell
Allele Type	Targeted (Conditional ready (e.g. floxed), Null/Knockout)
Allele Synonym(s)	Mc4r^tb; loxTB Mc4r
Gene Symbol and Name	Mc4r, melanocortin 4 receptor
Gene Synonym(s)	Fatboy; Glu3; Pkcp; Pkcp; glucose 3; pork chop
Strain of Origin	129S4/SvJae
Chromosome	18
Molecular Note	A loxP flanked PGK-neomycin selection marker inserted in the 5' UTR created a null allele. Cre recombinase deletes the selection marker, restoring normal activity of the allele. Mice fail to respond to MC4R agonist MTII. This is a null allele that can be "reactivated" by cre recombinase.
Mutations Made By	Bradford Lowell, Beth Israel Deaconess Med Cntr (Harvard)

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
- Hyperinsulinemia
- Obesity With Diabetes
- Obesity Without Diabetes
Neurobiology Research
- Metabolic Defects
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Diabetes and Obesity Research
  - loxP
- Metabolism Research
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

Genotype: Mc4r^tm1Lowl/Mc4r⁺
involves: 129S4/SvJae * C57BL/6

growth/size/body region phenotype

obese

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl
involves: 129S4/SvJae * C57BL/6J

growth/size/body region phenotype

increased body length
- at 12 weeks, homozygotes show increased snout-anus length

increased susceptibility to diet-induced obesity
- mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet

increased susceptibility to weight gain
- mutants exhibit increased weight gain compared to wild-type mice when fed either the standard diet or a high-fat diet

obese
- male and female homozygotes display severe early-onset obesity

homeostasis/metabolism phenotype

abnormal oxygen consumption
- mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do

decreased adiponectin level
- mutants fed the high-fat diet exhibit decreased serum adiponectin levels compared to wild-type mice on the same diet

decreased oxygen consumption
- oxygen consumption is reduced in the dark and light cycles compared to wild-type and is similar to mutants also expressing Tg(Sim1-cre)1Lowl

increased circulating alanine transaminase level
- mutants fed the high-fat diet show increased serum alanine aminotransferase concentrations compared to wild-type mice

increased circulating free fatty acid level
- mutants fed the high-fat diet show an increase in serum free fatty acid concentrations relative to wild-type mice

increased circulating insulin level
- hyperinsulinemia is displayed by homozygotes

increased circulating interleukin-6 level
- mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet

increased circulating leptin level
- mutants fed the high-fat diet exhibit increased serum leptin levels compared to wild-type mice on the same diet

increased liver triglyceride level
- livers of mutants fed the high-fat diet exhibit increased triglyceride secretion compared to wild-type livers
- mutants exhibit increased hepatic triglyceride content compared to wild-type mice on either the standard or high-fat diet

increased susceptibility to diet-induced obesity
- mutants exhibit increased weight gain compared to wild-type mice when fed a high-fat diet

behavior/neurological phenotype

abnormal food intake
- unlike wild-type mice, mutants do not exhibit a reduction in food intake after treatment with the Mc4r inhibitor, MTII

polyphagia
- obesity is accompanied by polyphagia

adipose tissue phenotype

adipose tissue inflammation
- white adipose tissue of mutants fed the high-fat diet for 8 weeks exhibits increased macrophage infiltration and pro-inflammatory cytokine expression compared to wild-type white adipose tissue

increased total body fat amount
- mutants fed the high-fat diet also exhibit increased adiposity, but only up to 8 weeks of high-fat feeding with no further increase after 8 weeks
- mutants fed the standard diet exhibit increased adiposity compared to wild-type mice on the same diet

immune system phenotype

adipose tissue inflammation
- white adipose tissue of mutants fed the high-fat diet for 8 weeks exhibits increased macrophage infiltration and pro-inflammatory cytokine expression compared to wild-type white adipose tissue

increased circulating interleukin-6 level
- mutants fed the high-fat diet exhibit increased serum IL-6 levels compared to wild-type mice on the same diet

liver inflammation
- livers from mutants fed the high-fat diet exhibit ballooning degeneration and massive infiltration of inflammatory cells
- livers from mutants fed the high-fat diet exhibit increased inflammatory cell infiltration compared to wild-type livers

liver/biliary system phenotype

hepatic steatosis
- mutants fed the high-fat diet develop liver steatosis faster (by 8 weeks of high-fat diet) than wild-type mice (by 20 weeks of high-fat diet)
- mutants fed the high-fat diet for 8 weeks exhibit massive microvesicular steatosis in the centrilobular and portal areas while wild-type mice only have minimal lipid accumulation in the liver

increased hepatocellular carcinoma incidence
- mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors
- tumors resemble hepatocellular carcinoma

increased liver triglyceride level
- livers of mutants fed the high-fat diet exhibit increased triglyceride secretion compared to wild-type livers
- mutants exhibit increased hepatic triglyceride content compared to wild-type mice on either the standard or high-fat diet

increased liver weight
- mutants exhibit increased liver weight compared to wild-type mice on either the standard or high-fat diet

liver fibrosis
- livers from mutants fed the high-fat diet exhibit increased pericellular fibrosis compared to wild-type mice at 8 and 20 weeks of high-fat feeding

liver inflammation
- livers from mutants fed the high-fat diet exhibit ballooning degeneration and massive infiltration of inflammatory cells
- livers from mutants fed the high-fat diet exhibit increased inflammatory cell infiltration compared to wild-type livers

neoplasm

increased hepatocellular carcinoma incidence
- mutants fed the high-fat diet, but not the standard diet, for a year develop liver tumors
- tumors resemble hepatocellular carcinoma

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl
involves: 129S4/SvJae

growth/size/body region phenotype

obese
- become obese but not hypertensive

The following phenotype relates to a compound genotype created using this strain

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Slc17a6^tm2(cre)Lowl/Slc17a6⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

growth/size/body region phenotype
- rescue of the increased weight gain, of the fat stores, of hyperphagia and of the increased linear length seen in single Mc4r homozygotes

homeostasis/metabolism phenotype

homeostasis/metabolism phenotype
- mice show normalization of the hyperglycemia and hyperinsulinemia that is seen in single Mc4r homozygotes

respiratory system phenotype

respiratory system phenotype
- rescue of the depressed respiratory exchange ratio seen in single Mc4r homozygotes

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Nes-cre)1Kln/0
involves: 129S4/SvJae * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected
- mice homozygous for reactivated Mc4r in neurons show normal body weights and rescue of the increased snout-anus length observed in Mc4r^tm1Lowl homozygotes

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB

growth/size/body region phenotype

growth/size/body region phenotype
- at 12 weeks, transgenic mice and wild-type littermates have the same snout-anus length, compared to increased length observed in nontransgenic Mc4r^tm1Lowl mice

increased body weight
- transgenic mice have increased fat mass compared with wild-type littermates, but significantly decreased fat mass compared to Mc4r^tm1Lowl littermates

increased lean body mass
- transgenic mice have increased lean mass compared with wild-type littermates, but significantly decreased lean mass compared to Mc4r^tm1Lowl littermates

obese
- at 12 weeks of age, male and female mutants have only 37% and 46% respectively, of the obesity observed in mice homozygous for Mc4r disruption

homeostasis/metabolism phenotype

abnormal oxygen consumption
- mice do not show an increase in oxygen consumption from stimulation by MTII as wild-type mice do

decreased oxygen consumption
- oxygen consumption is reduced in the dark and light cycles compared to wild-type and is similar to Mc4r^tm1Lowl homozygotes

behavior/neurological phenotype

abnormal food intake
- when treated with MTII an Mc4r inhibitor, wild-type mice show a 50% reduction in food intake, while transgenic mice display no effect on intake

behavior/neurological phenotype
- transgenic mice are obese, yet show food intake comparable to wild-type mice at 11 weeks of age

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Zp3-cre)3Mrt/0
involves: 129S4/SvJae * C57BL/6J * FVB/N

normal phenotype

no abnormal phenotype detected
- mice homozygous for reactivated Mc4r in neurons show normal body weights and rescue of the increased snout-anus length observed in Mc4r homozygotes
- mice homozygous for reactivated Mc4r in the germline show normal body weights and rescue of the increased snout-anus length observed in Mc4r^tm1Lowl homozygotes

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Oxt^{tm1.1(cre)Dolsn}/Oxt⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

growth/size/body region phenotype

obese

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Slc32a1^tm2(cre)Lowl/Slc32a1⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

obese

References

Balthasar N; Dalgaard LT; Lee CE; Yu J; Funahashi H; Williams T; Ferreira M; Tang V; McGovern RA; Kenny CD; Christiansen LM; Edelstein E; Choi B; Boss O; Aschkenasi C; Zhang CY; Mountjoy K; Kishi T; Elmquist JK; Lowell BB. 2005. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123(3):493-505. PubMed: 16269339 MGI: J:115192

Additional - Mc4r^tm1Lowl related

Arble DM; Holland J; Ottaway N; Sorrell J; Pressler JW; Morano R; Woods SC; Seeley RJ; Herman JP; Sandoval DA; Perez-Tilve D. 2015. The melanocortin-4 receptor integrates circadian light cues and metabolism. Endocrinology 156(5):1685-91. PubMed: 25730108 MGI: J:222118
Arteaga-Solis E; Zee T; Emala CW; Vinson C; Wess J; Karsenty G. 2013. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab 17(1):35-48. PubMed: 23312282 MGI: J:195073
Asai M; Ramachandrappa S; Joachim M; Shen Y; Zhang R; Nuthalapati N; Ramanathan V; Strochlic DE; Ferket P; Linhart K; Ho C; Novoselova TV; Garg S; Ridderstrale M; Marcus C; Hirschhorn JN; Keogh JM; O'Rahilly S; Chan LF; Clark AJ; Farooqi IS; Majzoub JA. 2013. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 341(6143):275-8. PubMed: 23869016 MGI: J:199365
Chaly AL; Srisai D; Gardner EE; Sebag JA. 2016. The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1. Elife 5:. PubMed: 26829592 MGI: J:230718
Cui H; Lutter M. 2013. The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine. Genes Brain Behav 12(6):658-65. PubMed: 23786641 MGI: J:213389
Cui H; Mason BL; Lee C; Nishi A; Elmquist JK; Lutter M. 2012. Melanocortin 4 receptor signaling in dopamine 1 receptor neurons is required for procedural memory learning. Physiol Behav 106(2):201-10. PubMed: 22342812 MGI: J:227615
Gao Y; Ottaway N; Schriever SC; Legutko B; Garcia-Caceres C; de la Fuente E; Mergen C; Bour S; Thaler JP; Seeley RJ; Filosa J; Stern JE; Perez-Tilve D; Schwartz MW; Tschop MH; Yi CX. 2014. Hormones and diet, but not body weight, control hypothalamic microglial activity. Glia 62(1):17-25. PubMed: 24166765 MGI: J:203061
Goncalves GH; Li W; Garcia AV; Figueiredo MS; Bjorbaek C. 2014. Hypothalamic agouti-related peptide neurons and the central melanocortin system are crucial mediators of leptin's antidiabetic actions. Cell Rep 7(4):1093-103. PubMed: 24813890 MGI: J:211797
Guan X; Shi X; Li X; Chang B; Wang Y; Li D; Chan L. 2012. GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility. Am J Physiol Endocrinol Metab 303(7):E853-64. PubMed: 22829581 MGI: J:189593
Itoh M; Kato H; Suganami T; Konuma K; Marumoto Y; Terai S; Sakugawa H; Kanai S; Hamaguchi M; Fukaishi T; Aoe S; Akiyoshi K; Komohara Y; Takeya M; Sakaida I; Ogawa Y. 2013. Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans. PLoS One 8(12):e82163. PubMed: 24349208 MGI: J:209729
Itoh M; Suganami T; Nakagawa N; Tanaka M; Yamamoto Y; Kamei Y; Terai S; Sakaida I; Ogawa Y. 2011. Melanocortin 4 receptor-deficient mice as a novel mouse model of nonalcoholic steatohepatitis. Am J Pathol 179(5):2454-63. PubMed: 21906580 MGI: J:177386
Karlsson-Lindahl L; Schmidt L; Haage D; Hansson C; Taube M; Egeciouglu E; Tan YX; Admyre T; Jansson JO; Vlodavsky I; Li JP; Lindahl U; Dickson SL. 2012. Heparanase affects food intake and regulates energy balance in mice. PLoS One 7(3):e34313. PubMed: 22479599 MGI: J:187121
Kawahara Y; Grimberg A; Teegarden S; Mombereau C; Liu S; Bale TL; Blendy JA; Nishikura K. 2008. Dysregulated editing of serotonin 2C receptor mRNAs results in energy dissipation and loss of fat mass. J Neurosci 28(48):12834-44. PubMed: 19036977 MGI: J:142503
Konuma K; Itoh M; Suganami T; Kanai S; Nakagawa N; Sakai T; Kawano H; Hara M; Kojima S; Izumi Y; Ogawa Y. 2015. Eicosapentaenoic acid ameliorates non-alcoholic steatohepatitis in a novel mouse model using melanocortin 4 receptor-deficient mice. PLoS One 10(3):e0121528. PubMed: 25816330 MGI: J:229262
Krashes MJ; Shah BP; Koda S; Lowell BB. 2013. Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP. Cell Metab 18(4):588-95. PubMed: 24093681 MGI: J:206003
Lute B; Jou W; Lateef DM; Goldgof M; Xiao C; Pinol RA; Kravitz AV; Miller NR; Huang YG; Girardet C; Butler AA; Gavrilova O; Reitman ML. 2014. Biphasic effect of melanocortin agonists on metabolic rate and body temperature. Cell Metab 20(2):333-45. PubMed: 24981835 MGI: J:215467
Nogueiras R; Wiedmer P; Perez-Tilve D; Veyrat-Durebex C; Keogh JM; Sutton GM; Pfluger PT; Castaneda TR; Neschen S; Hofmann SM; Howles PN; Morgan DA; Benoit SC; Szanto I; Schrott B; Schurmann A; Joost HG; Hammond C; Hui DY; Woods SC; Rahmouni K; Butler AA; Farooqi IS; O'Rahilly S; Rohner-Jeanrenaud F; Tschop MH. 2007. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 117(11):3475-88. PubMed: 17885689 MGI: J:127528
Ottaway N; Mahbod P; Rivero B; Norman LA; Gertler A; D'Alessio DA; Perez-Tilve D. 2015. Diet-induced obese mice retain endogenous leptin action. Cell Metab 21(6):877-82. PubMed: 25980347 MGI: J:226133
Pillot B; Duraffourd C; Begeot M; Joly A; Luquet S; Houberdon I; Naville D; Vigier M; Gautier-Stein A; Magnan C; Mithieux G. 2011. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice. PLoS One 6(4):e19107. PubMed: 21544212 MGI: J:172374
Rossi J; Balthasar N; Olson D; Scott M; Berglund E; Lee CE; Choi MJ; Lauzon D; Lowell BB; Elmquist JK. 2011. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab 13(2):195-204. PubMed: 21284986 MGI: J:169562
Samuelsson AS; Mullier A; Maicas N; Oosterhuis NR; Eun Bae S; Novoselova TV; Chan LF; Pombo JM; Taylor PD; Joles JA; Coen CW; Balthasar N; Poston L. 2016. Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity. Proc Natl Acad Sci U S A 113(43):12298-12303. PubMed: 27791019 MGI: J:238802
Shah BP; Vong L; Olson DP; Koda S; Krashes MJ; Ye C; Yang Z; Fuller PM; Elmquist JK; Lowell BB. 2014. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc Natl Acad Sci U S A 111(36):13193-8. PubMed: 25157144 MGI: J:216397
Shen Y; Tian M; Zheng Y; Gong F; Fu AK; Ip NY. 2016. Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer's Disease Model. Cell Rep 17(7):1819-1831. PubMed: 27829153 MGI: J:242331
Sohn JW; Harris LE; Berglund ED; Liu T; Vong L; Lowell BB; Balthasar N; Williams KW; Elmquist JK. 2013. Melanocortin 4 receptors reciprocally regulate sympathetic and parasympathetic preganglionic neurons. Cell 152(3):612-9. PubMed: 23374353 MGI: J:193452
Thiebaud N; Johnson MC; Butler JL; Bell GA; Ferguson KL; Fadool AR; Fadool JC; Gale AM; Gale DS; Fadool DA. 2014. Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning. J Neurosci 34(20):6970-84. PubMed: 24828650 MGI: J:211263
Vella KR; Ramadoss P; Lam FS; Harris JC; Ye FD; Same PD; O'Neill NF; Maratos-Flier E; Hollenberg AN. 2011. NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways. Cell Metab 14(6):780-90. PubMed: 22100407 MGI: J:179670
Voss-Andreae A; Murphy JG; Ellacott KL; Stuart RC; Nillni EA; Cone RD; Fan W. 2007. Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology 148(4):1550-60. PubMed: 17194736 MGI: J:129583
Xu Y; Jones JE; Lauzon DA; Anderson JG; Balthasar N; Heisler LK; Zinn AR; Lowell BB; Elmquist JK. 2010. A serotonin and melanocortin circuit mediates D-fenfluramine anorexia. J Neurosci 30(44):14630-4. PubMed: 21048120 MGI: J:166702
Xu Y; Kim ER; Fan S; Xia Y; Xu Y; Huang C; Tong Q. 2014. Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists. Biochem Biophys Res Commun 451(2):184-9. PubMed: 25065745 MGI: J:220129
Xu Y; Wu Z; Sun H; Zhu Y; Kim ER; Lowell BB; Arenkiel BR; Xu Y; Tong Q. 2013. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab 18(6):860-70. PubMed: 24315371 MGI: J:206137
Zhang Z; Turer E; Li X; Zhan X; Choi M; Tang M; Press A; Smith SR; Divoux A; Moresco EM; Beutler B. 2016. Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice. Proc Natl Acad Sci U S A 113(42):E6418-E6426. PubMed: 27708159 MGI: J:236520
do Carmo JM; da Silva AA; Rushing JS; Pace B; Hall JE. 2013. Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons. Am J Physiol Regul Integr Comp Physiol 305(4):R359-68. PubMed: 23842677 MGI: J:201516

Also Known As: loxTB Mc4r

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Mc4rtm1Lowl

Allele Symbol: Mc4rtm1Lowl

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Mc4rtm1Lowl/Mc4r+involves: 129S4/SvJae * C57BL/6

growth/size/body region phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowlinvolves: 129S4/SvJae * C57BL/6J

growth/size/body region phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

adipose tissue phenotype

immune system phenotype

liver/biliary system phenotype

neoplasm

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowlinvolves: 129S4/SvJae

growth/size/body region phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Slc17a6tm2(cre)Lowl/Slc17a6+involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

homeostasis/metabolism phenotype

respiratory system phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Tg(Nes-cre)1Kln/0involves: 129S4/SvJae * C57BL/6 * SJL

normal phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Tg(Sim1-cre)1Lowl/0involves: 129S4/SvJae * C57BL/6J * FVB

growth/size/body region phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Tg(Zp3-cre)3Mrt/0involves: 129S4/SvJae * C57BL/6J * FVB/N

normal phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Oxttm1.1(cre)Dolsn/Oxt+involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

growth/size/body region phenotype

Genotype: Mc4rtm1Lowl/Mc4rtm1Lowl Slc32a1tm2(cre)Lowl/Slc32a1+involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

growth/size/body region phenotype

References

Additional - Mc4rtm1Lowl related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

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Mc4r^tm1Lowl

Allele Symbol: Mc4r^tm1Lowl

Genotype: Mc4r^tm1Lowl/Mc4r⁺
involves: 129S4/SvJae * C57BL/6

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl
involves: 129S4/SvJae * C57BL/6J

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl
involves: 129S4/SvJae

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Slc17a6^tm2(cre)Lowl/Slc17a6⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Nes-cre)1Kln/0
involves: 129S4/SvJae * C57BL/6 * SJL

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Sim1-cre)1Lowl/0
involves: 129S4/SvJae * C57BL/6J * FVB

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Tg(Zp3-cre)3Mrt/0
involves: 129S4/SvJae * C57BL/6J * FVB/N

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Oxt^{tm1.1(cre)Dolsn}/Oxt⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6

Genotype: Mc4r^tm1Lowl/Mc4r^tm1Lowl Slc32a1^tm2(cre)Lowl/Slc32a1⁺
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * FVB/N

Additional - Mc4r^tm1Lowl related