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| Magel2-null mice harbor a maternally-inherited imprinted/silenced wildtype allele and a paternally-inherited Magel2-lacZ knock-in allele that also abolishes endogenous Magel2 (melanoma antigen, family L, 2) gene function. Magel2-null mice on this C57BL/6J genetic background recapitulate some aspects of Prader-Willi syndrome, and may be useful in studying disorders of the suprachiasmatic nuclei, circadian rhythms, obesity, and growth and feeding regulation. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
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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 Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Rachel Wevrick, University of Alberta Description
The mouse locus 7qB4/B5 (syntenic with the Prader-Willi region at chromosome position 15q11-q13 in humans) encompasses the cluster of paternally-expressed imprinted genes Magel2, Ndn, Mkrn3, and Peg12. As maternal imprinting silences the Magel2 allele, only the paternally inherited Magel2 allele is expressed. The Magel2-lacZ knock-in allele abolishes endogenous gene function and expresses a β-galactosidase fusion protein. Under control of the upstream promoter/enhancer elements, lacZ expression is directed to the same tissues as the wildtype gene. For example, β-galactosidase expression during embryogenesis is detected in central nervous system (neural tube, forebrain, midbrain and embryonic hypothalamus), peripheral nervous system (dorsal root ganglia and peripheral neurons innervating limb and trunk muscles), and some non-neuronal tissues (genital tubercle, midgut region and placenta). Adult β-galactosidase expression in the brain is most prominent in the magnocellular system (composed of suprachiasmatic nuclei (SCN), paraventricular nuclei (PVN) and supraoptic nuclei (SON)) of the hypothalamus. The donating investigator breeds heterozygous females with wildtype males (or C57BL/6J inbred males) to maintain the line; as the resulting offspring will have no abnormal phenotype. To obtain "Magel2-null" offspring (both maternal and paternal Magel2 alleles are non-functional), wildtype females are bred with heterozygous males; allowing maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Magel2-lacZ (null) allele. Magel2-null mice have disrupted circadian rhythm and metabolism associated with reductions in embryonic/perinatal survival, total activity, food consumption, weight before weaning, and fertility in both sexes, as well as increased adiposity after weaning and altered reproductive behavior. Magel2-null mice on this C57BL/6J genetic background recapitulate some aspects of Prader-Willi syndrome, and may be useful in studying disorders of the suprachiasmatic nuclei, circadian rhythms, obesity, and growth and feeding regulation.Development
A targeting vector was designed to replace the open reading frame of the Magel2 (melanoma antigen, family L, 2) locus with a β-galactosidase (lacZ) expression cassette and loxP-flanked neo cassette. The construct was electroporated into C57BL/6-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to establish the colony. Mice were then backcrossed to C57BL/6J for approximately 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (256 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Prader-Willi Syndrome; PWS
assigned by genotype
Magel2tm1Stw/Magel2+
C57BL/6-Magel2tm1Stw
- mortality/aging
- early reproductive senescence
- infertility occurs in both sexes by 24 weeks of age in mice that inherit the mutant allele paternally (MGI Ref ID J:144836)
- fertility rates are normal between 7-14 weeks of age, drops to about 20% at 19-24 weeks of age, with no litters are born after 24 weeks of age (MGI Ref ID J:144836)
- at younger ages, there is also a significant increase in the mean time between pairing and successful breeding (males: 9 days vs. 4 days for controls, females: 12 days vs. 4 days in controls) (MGI Ref ID J:144836)
- partial postnatal lethality
- only 50-60% of pups born to female mice that inherit the mutant allele paternally survive until weaning (MGI Ref ID J:144836)
- cellular phenotype
- maternal imprinting
- only the paternally inherited allele is expressed (MGI Ref ID J:144836)
- reproductive system phenotype
- abnormal corpus luteum morphology
- an absence of corpus lutea is noted in 10 of 14 female mice that are over 24 weeks of age and have inherited the mutant allele paternally (MGI Ref ID J:144836)
- abnormal proestrus
- only 25% of mice experience proestrus in female mice that are 26 weeks of age and have inherited the mutant allele paternally (MGI Ref ID J:144836)
- decreased litter size
- a mean of 6.4 pups is born to female mice that inherit the mutant allele paternally compared to 7.8 pups for controls (MGI Ref ID J:144836)
- delayed vaginal opening
- in female mice inheriting the mutant allele paternally, vaginal opening is significantly delayed by 1.4 days (MGI Ref ID J:144836)
- early reproductive senescence
- infertility occurs in both sexes by 24 weeks of age in mice that inherit the mutant allele paternally (MGI Ref ID J:144836)
- fertility rates are normal between 7-14 weeks of age, drops to about 20% at 19-24 weeks of age, with no litters are born after 24 weeks of age (MGI Ref ID J:144836)
- at younger ages, there is also a significant increase in the mean time between pairing and successful breeding (males: 9 days vs. 4 days for controls, females: 12 days vs. 4 days in controls) (MGI Ref ID J:144836)
- late onset of menarche
- in female mice inheriting the mutant allele paternally, the age of first estrus is delayed by 5.3 days (MGI Ref ID J:144836)
- prolonged estrous cycle
- estrous cycle is prolonged and irregular in female mice that have inherited the mutant allele paternally (MGI Ref ID J:144836)
- taste/olfaction phenotype
- impaired olfaction
- latency time to find buried food is more than twice that of controls for mice that are over 24 weeks of age and have inherited the mutant allele paternally (MGI Ref ID J:144836)
- fasted male mice that have inherited the mutant allele paternally only investigate a dried vanilla spot for 0.75 s compared to 6.7 s for controls (MGI Ref ID J:144836)
- sexually-experienced male mice that have inherited the mutant allele paternally show no preference for female soiled bedding unlike their wild-type controls (MGI Ref ID J:144836)
- behavior/neurological phenotype
- pup cannibalization
- female mice with paternal inheritance of the mutant allele frequently cannibalize their pups (MGI Ref ID J:144836)
- endocrine/exocrine gland phenotype
- abnormal corpus luteum morphology
- an absence of corpus lutea is noted in 10 of 14 female mice that are over 24 weeks of age and have inherited the mutant allele paternally (MGI Ref ID J:144836)
- homeostasis/metabolism phenotype
- decreased circulating testosterone level
- mean serum testosterone levels are significantly lower in male mice that inherit the mutant allele paternally (6.1 ng/ml versus 20.2 ng/ml in controls) (MGI Ref ID J:144836)
Magel2tm1Stw/Magel2tm1Stw
C57BL/6-Magel2tm1Stw
- mortality/aging
- partial postnatal lethality
- when the Magel2tm1Stw allele is inherited paternally, 10% fewer mice survive to weaning than expected (MGI Ref ID J:125637)
- reproductive system phenotype
- reduced male fertility
- behavior/neurological phenotype
- abnormal circadian rhythm
- when the Magel2tm1Stw allele is inherited paternally, mice run significantly less than wild-type mice (3047+/-930 counts per day compared to 12770+/-2343 counts per day for wild-type mice) (MGI Ref ID J:125637)
- when the Magel2tm1Stw allele is inherited paternally, mice run in more frequent and shorter bouts (8.5+/-0.7 bouts per day compared to 4.9+/-0.4 bouts per day for wild-type mice and 21.8+/-4.3 minutes per bout compared to 83.1+/-15.4 minutes per bout for wild-type mice) (MGI Ref ID J:125637)
- when the Magel2tm1Stw allele is inherited paternally, mice exhibit less daily activity during the subjective night (76.9+/-2.8% compared to 86.6+/-2.5% for wild-type mice)when the Magel2tm1Stw allele is inherited paternally, mice exhibit less daily activity during the subjective night (76.9+/-2.8% compared to 86.6+/-2.5% for wild-type mice) (MGI Ref ID J:125637)
- when the Magel2tm1Stw allele is inherited paternally, rhythms have lower chi-squared periodogram amplitudes than in wild-type mice (MGI Ref ID J:125637)
- decreased compensatory feeding amount
- when the Magel2tm1Stw allele is inherited paternally, after 24 hours starvation mice consume less food than wild-type mice (MGI Ref ID J:125637)
- hypoactivity
- when the Magel2tm1Stw allele is inherited paternally, mice run significantly less than wild-type mice (3047+/-930 counts per day compared to 12770+/-2343 counts per day for wild-type mice) (MGI Ref ID J:125637)
- when the Magel2tm1Stw allele is inherited paternally, mice run in more frequent and shorter bouts (8.5+/-0.7 bouts per day compared to 4.9+/-0.4 bouts per day for wild-type mice and 21.8+/-4.3 minutes per bout compared to 83.1+/-15.4 minutes per bout for wild-type mice) (MGI Ref ID J:125637)
- growth/size phenotype
- *normal* growth/size phenotype
- when the Magel2tm1Stw allele is inherited paternally, surviving mice display no abnormalities in size or weight up to 2 years of age (MGI Ref ID J:125637)
- cellular phenotype
- maternal imprinting
- only the paternally inherited allele is expressed (MGI Ref ID J:125637)
This mouse can be used to support research in many areas including:
Developmental Biology Research
Embryonic Lethality (Homozygous)
incomplete
Growth Defects
Growth Defects (homozygous)
Imprinting
Perinatal Lethality
Homozygous
Diabetes and Obesity Research
Obesity Without Diabetes
Endocrine Deficiency Research
Hypothalamus/Pituitary Defects
Neurobiology Research
lacZ expression in neural tissue
Behavioral and Learning Defects
Circadian Rhythms
Metabolic Defects
Reproductive Biology Research
Fertility Defects
Research Tools
lacZ Expression
Developmental Biology Research
transplantation marker for embryonic and adult tissue
Diabetes and Obesity Research
lacZ
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: multiple
Tissue/Cell Markers: neurons
Metabolism Research
Neurobiology Research
cell marker
Reproductive Biology Research
transplantation marker for embryonic and adult tissue
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Magel2tm1Stw | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Colin L Stewart | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Magel2-; | ||
| Mutation Made By | Rachel Wevrick, University of Alberta | ||
| Strain of Origin | B6.Cg-Thy1 | ||
| ES Cell Line Name | Bruce 4 | ||
| ES Cell Line Strain | B6.Cg-Thy1 | ||
| Site of Expression | lacZ is expressed during embryogenesis in the central nervous system, peripheral nervous system, and some non-neuronal tissues including the genital tubercle, midgut region and placenta. Adult lacZ expression in the brain is most prominent in the magnocellular system, paraventricular nuclei (PVN) and supraoptic nuclei (SON)) of the hypothalamus. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | The entire open reading frame was replaced with a lacZ-neo cassette. The endogenous promoter drives the expression of lacZ as confirmed by a beta-galactosidase assay. The absence of the paternal transcript was confirmed by RT-PCR. [MGI Ref ID J:125637] | ||
| Gene Symbol and Name | Magel2, melanoma antigen, family L, 2 | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | Mage-l2; NDNL1; nM15; ns7; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Magel2tm1Stw STD PCR, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Kozlov SV; Bogenpohl JW; Howell MP; Wevrick R; Panda S; Hogenesch JB; Muglia LJ; Van Gelder RN; Herzog ED; Stewart CL. 2007. The imprinted gene Magel2 regulates normal circadian output. Nat Genet 39(10):1266-72. [PubMed: 17893678] [MGI Ref ID J:125637]
Mercer RE; Wevrick R. 2009. Loss of magel2, a candidate gene for features of prader-willi syndrome, impairs reproductive function in mice. PLoS ONE 4(1):e4291. [PubMed: 19172181] [MGI Ref ID J:144836]
Additional References
Magel2tm1Stw relatedBischof JM; Stewart CL; Wevrick R. 2007. Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome. Hum Mol Genet 16(22):2713-9. [PubMed: 17728320] [MGI Ref ID J:129971]
Tennese AA; Wevrick R. 2011. Impaired hypothalamic regulation of endocrine function and delayed counterregulatory response to hypoglycemia in Magel2-null mice. Endocrinology 152(3):967-78. [PubMed: 21248145] [MGI Ref ID J:173876]
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, G200.Colony Maintenance
Breeding & Husbandry Maternal imprinting silences the Magel2 gene. Breeding heterozygous females with wildtype males (or C57BL/6J inbred males) results in offspring with no abnormal phenotype; this is desirable for routine colony maintenance. To obtain "Magel2-null" offspring (both maternal and paternal Magel2 alleles are non-functional), wildtype females are bred with heterozygous males; allowing maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Magel2-lacZ (null) allele. Magel2-null mice have reduced embryonic/perinatal survival and diminished fertility in both sexes.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
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.Ordering Information
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