Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N1pN1 Generation Definitions   Donating Investigator Ute Hochgeschwender,   Oklahoma Medical Research Foundation

Description
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. 60 to 75% of homozygotes die perinatally. Surviving homozygotes have decreased fertility and homozygous females produce milk that does not allow pups to survive past 14 days of age. No serum adrenocorticotropic hormone (ACTH) or corticosterone was detected by radioimmunoassay (RIA) of homozygotes. Serum epinephrine and aldosterone levels are reduced. Although homozygotes are born with adrenal glands or normal size, adrenal glands fail to grow postnatally and become almost undetectable with age. By 3 months of age, mice homozygous for the mutation are twice the weight of wildtype controls and increased serum leptin levels. Heterozygotes exhibit elevated serum leptin levels, but not increased weight and reduced levels of serum adrenocorticotropic hormone (ACTH), corticosterone, and aldosterone levels. Both heterozygotes and homozygotes have yellowish coat color; homozygotes have completely yellow pigmented bellies. Homozygous mutant mice have a higher intake of food and gain weight faster than wild-type controls when fed a high fat diet. Although homozygotes exhibit normal insulin serum levels, normal glucose fasting levels, and normal glucose clearance in glucose tolerance tests, they fail to recover from insulin induced hypoglycemia. On the 129S6/SvEvTac background, both homozygotes and heterozygotes develop pituitary gland tumors and reduced survival rates. On the C57BL/6 background, the donating investigator reports that mutants develop pituitary tumors after 12 months of age. This mutant mouse strain may be useful in studies of obesity, energy homeostasis, glucose homeostasis and endocrinology.

Development
A targeting vector containing a neomycin resistance gene was used to disrupt exon 3. The construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice, and then backcrossed to C57BL/6NHsd for 10 generations. After arriving at The Jackson Laboratory the mice were crossed to C57BL/6NJ for one generation.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pomc

003191	B6.129S2-Pomctm1Low/J
008322	B6.Cg-Tg(Pomc-MAPT/Topaz)1Rck/J
010714	B6.FVB-Tg(Pomc-cre)1Stl/J
009593	C57BL/6J-Tg(Pomc-EGFP)1Low/J
008326	FVB-Tg(Pomc-rtTA)1Rck/J
006421	FVB-Tg(Pomc1-hrGFP)1Lowl/J
005965	STOCK Tg(Pomc1-cre)16Lowl/J

View Strains carrying other alleles of Pomc     (7 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Proopiomelanocortin Deficiency - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Pomc^tm2Ute/Pomc⁺

        involves: 129S1/SvEv * 129X1/SvJ

• homeostasis/metabolism phenotype
• increased circulating leptin level   (MGI Ref ID J:57503)
• growth/size phenotype
• *normal* growth/size phenotype
  • although serum leptin levels are increased, mutants do not show an increase in body weight   (MGI Ref ID J:57503)

Pomc^tm2Ute/Pomc^tm2Ute

        involves: 129S1/SvEv * 129X1/SvJ

• mortality/aging
• partial prenatal lethality
  • homozygotes are born to heterozygous parents at 1/4 the frequency expected   (MGI Ref ID J:57503)
• growth/size phenotype
• increased body length
  • the weight gain in accompanied by a slight, but significant, increase in body length   (MGI Ref ID J:57503)
• increased susceptibility to diet-induced obesity
  • mutants show an increased rate of weight gain on a high fat diet   (MGI Ref ID J:57503)
• obese
  • mutants begin gaining weight in the second month after birth and by the third month of age, they are about twice the weight of wild-type   (MGI Ref ID J:57503)
  • mice treated with a stable alpha-melanocyte-stimulating hormone agonist lost more than 40% of their excess weight in 2 weeks   (MGI Ref ID J:57503)
• pigmentation phenotype
• diluted coat color   (MGI Ref ID J:57503)
• yellow coat color
  • coat covering the sides and belly is more yellow than in wild-type and the tips of the hairs at the back have a more yellowish tinge   (MGI Ref ID J:57503)
• endocrine/exocrine gland phenotype
• absent adrenal gland   (MGI Ref ID J:57503)
• homeostasis/metabolism phenotype
• decreased circulating adrenaline level   (MGI Ref ID J:57503)
• decreased circulating adrenocorticotropin level   (MGI Ref ID J:57503)
• decreased circulating aldosterone level
  • serum aldosterone is below detectable levels   (MGI Ref ID J:57503)
• decreased circulating corticosterone level
  • serum corticosterone is below detectable levels   (MGI Ref ID J:57503)
• increased circulating leptin level
  • weight gain is accompanied by a large increase in serum leptin levels   (MGI Ref ID J:57503)
• increased dopamine level
  • dopamine levels are slightly higher   (MGI Ref ID J:57503)
• increased susceptibility to diet-induced obesity
  • mutants show an increased rate of weight gain on a high fat diet   (MGI Ref ID J:57503)
• behavior/neurological phenotype
• increased eating behavior
  • mutants have a greater food intake than wild-type on both a regular or high-fat diet   (MGI Ref ID J:57503)
• nervous system phenotype
• increased dopamine level
  • dopamine levels are slightly higher   (MGI Ref ID J:57503)
• integument phenotype
• diluted coat color   (MGI Ref ID J:57503)
• yellow coat color
  • coat covering the sides and belly is more yellow than in wild-type and the tips of the hairs at the back have a more yellowish tinge   (MGI Ref ID J:57503)

View Research Applications

Research Applications

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

Endocrine Deficiency Research
Adrenal Cortex Defects
Adrenal Medulla Defects

Mouse/Human Gene Homologs
obesity, adrenal insufficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Pomctm2Ute
Allele Name		targeted mutation 2, Ute Hochgeschwender
Allele Type		Targeted (knock-out)
Mutation Made By		Ute Hochgeschwender,   Oklahoma Medical Research Foundation
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Pomc, pro-opiomelanocortin-alpha
Chromosome		12
Gene Common Name(s)		ACTH; BE; CLIP; LPH; MSH; NPP; POC; Pomc-1; Pomc1; Pomc2; adrenal corticotropic hormone; alpha-MSH; alpha-melanocyte stimulating hormone; alphaMSH; beta-MSH; beta-endorphin; beta-melanocyte stimulating hormone; gamma-MSH; gamma-melanocyte stimulating hormone;
Molecular Note		Exon 3 was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded all but the first 44 residues of the preprotein (all but 18 residues of the mature protein). [MGI Ref ID J:57503]

Genotyping

Genotyping Information

Genotyping Protocols

Pomc^tm2Ute, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yaswen L; Diehl N; Brennan MB; Hochgeschwender U. 1999. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin [see comments] Nat Med 5(9):1066-70. [PubMed: 10470087]  [MGI Ref ID J:57503]

Additional References

Pomc^tm2Ute related

Costa JL; Forbes S; Brennan MB; Hochgeschwender U. 2011. Genetic modifications of mouse proopiomelanocortin peptide processing. Mol Cell Endocrinol 336(1-2):14-22. [PubMed: 21195130]  [MGI Ref ID J:179466]

Hochgeschwender U; Costa JL; Reed P; Bui S; Brennan MB. 2003. Altered glucose homeostasis in proopiomelanocortin-null mouse mutants lacking central and peripheral melanocortin. Endocrinology 144(12):5194-202. [PubMed: 12970157]  [MGI Ref ID J:87246]

Karpac J; Czyzewska K; Kern A; Brush RS; Anderson RE; Hochgeschwender U. 2008. Failure of adrenal corticosterone production in POMC-deficient mice results from lack of integrated effects of POMC peptides on multiple factors. Am J Physiol Endocrinol Metab 295(2):E446-55. [PubMed: 18559987]  [MGI Ref ID J:139994]

Karpac J; Ostwald D; Bui S; Hunnewell P; Shankar M; Hochgeschwender U. 2005. Development, maintenance, and function of the adrenal gland in early postnatal proopiomelanocortin-null mutant mice. Endocrinology 146(6):2555-62. [PubMed: 15731356]  [MGI Ref ID J:109471]

Karpac J; Ostwald D; Li GY; Bui S; Hunnewell P; Brennan MB; Hochgeschwender U. 2006. Proopiomelanocortin heterozygous and homozygous null mutant mice develop pituitary adenomas. Cell Mol Biol (Noisy-le-grand) 52(2):47-52. [PubMed: 16914086]  [MGI Ref ID J:115999]

Linhart KB; Majzoub JA. 2008. Pomc knockout mice have secondary hyperaldosteronism despite an absence of adrenocorticotropin. Endocrinology 149(2):681-6. [PubMed: 17991729]  [MGI Ref ID J:141451]

Saedler K; Hochgeschwender U. 2011. Impaired neonatal survival of pro-opiomelanocortin null mutants. Mol Cell Endocrinol 336(1-2):6-13. [PubMed: 21184805]  [MGI Ref ID J:179468]

Slominski A; Plonka PM; Pisarchik A; Smart JL; Tolle V; Wortsman J; Low MJ. 2005. Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice on a nonagouti (a/a) genetic background. Endocrinology 146(3):1245-53. [PubMed: 15564334]  [MGI Ref ID J:129805]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. 60 to 75% of homozygotes die perinatally. Surviving homozygotes have decreased fertility and homozygous females produce milk that does not allow pups to survive past 14 days of age. The donating investigator uses a heterozygote x wildtype breeding scheme to maintain this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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