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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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 N8p
Generation DefinitionsDonating Investigator James R. Lupski, Baylor College of Medicine Description
Mice are albino. Heterozygous mice are viable and fertile and weigh slightly less than wildtype at 0-2 weeks of age. RT-PCR shows a blunted N-terminal product in kidney tissues that does not contain the two nuclear localization signals (NLS) or zinc finger like plant homeo domain (PHD). Heterozygous embryos have differential tissue expression of lacZ during development, faithfully recapitulating the expression pattern of Rai1. Less than 5% of heterozygous mice exhibit polydactyly. While noticeably smaller at 4-7 weeks, heterozygotes are significantly obese by 20-23 weeks. 7-18% of heterozygotes have craniofacial defects (broader and shorter nasal bone and lateral bending of the snout). The vast majority of homozygotes are embryonic lethal, with death occurring after implantation but before 15.5 days post coitum (during gastrulation and organogenesis). All homozygotes surviving to birth exhibit growth retardation and premature death with most dying before wean. Homozygous mice have shorter snouts and extra cartilaginous elements in digit 5 of both forelimbs. Craniofacial abnormalities are more severe in homozygotes than in heterozygotes. In addition, homozygotes have hypoplastic thyroid bones and axial skeleton defects not observed in heterozygotes (thinner and non-articulate 13th rib, axis-atlas fusion, defective closure of the dorsal arches, and transverse foramina of thoracic vertebra). This mouse may be useful in studies of obesity and craniofacial abnormalities, and is a model for Smith-Magenis syndrome (SMS).Development
A targeting vector containing an internal ribosome entry site-linked beta-galactosidase (lacZ) gene followed by a loxP-flanked PGKneo cassette was used to replace a large region of exon 2 (encoding amino acids 537-1790) of the endogenous gene. The construct was electroporated into 129S7/SvEvBrd-derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6-Tyrc-Brd blastocysts. The resulting chimeric males were bred to C57BL/6-Tyrc-Brd females and maintained on that background for at least 7 generations before arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred once to Stock No. 000058 (C57BL/6J-Tyrc-2J/J) and then maintained by mating heterozygotes.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (255 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).
Smith-Magenis Syndrome; SMS
assigned by genotype
Rai1tm1Jrl/Rai1+
B6.129S7-Rai1tm1Jrl/J
- growth/size phenotype
- obese
- although at 5 weeks of age, males are smaller than wild-type, by 10 and 15 weeks of age, no weight differences are seen between mutants and wild-type, and by 20 weeks of age, males are significantly larger than wild-type males (MGI Ref ID J:164451)
- females begin to gain weight around 20 weeks of age and are significantly larger at 25 and 30 weeks of age (MGI Ref ID J:164451)
- rate of weight gain in about 2-fold that of wild-type (MGI Ref ID J:164451)
- mice do not exhibit ketonuria or differences in insulin or glucose levels (MGI Ref ID J:164451)
- adipose tissue phenotype
- abnormal abdominal fat pad morphology
- increased white adipose tissue amount
- increase in white adipose tissue in females, with substantial adipose tissue found in thoracic cavity of older females and substantial fat stores around abdominal organs (MGI Ref ID J:164451)
- behavior/neurological phenotype
- abnormal circadian rhythm
- at 15 weeks of age, mice consume a higher proportion of their food during the light phase (rest phase) than wild-type mice (MGI Ref ID J:164451)
- increased food intake
- fasting studies show a delayed satiation response compared to wild-type mice; mutants continue to eat larger amounts even 60 hours after fasting when wild-type return to normal levels of eating (MGI Ref ID J:164451)
- polyphagia
- mutants are hyperphagic at 20 and 25 weeks, consuming about 50% more food than wild-type (MGI Ref ID J:164451)
- at 15 weeks of age, mice consume more food even though their weight is no different from wild-type (MGI Ref ID J:164451)
- at 15 weeks of age, mice consume a higher proportion of their food during the light phase (rest phase) than wild-type mice (MGI Ref ID J:164451)
- homeostasis/metabolism phenotype
- abnormal circulating hormone level
- increase in serum amylin levels in fasted mice older than 30 weeks of age (MGI Ref ID J:164451)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Rai1tm1Jrl/Rai1+
involves: 129S/SvEvBrd * C57BL/6
- growth/size phenotype
- decreased body weight
- underweight at 4-7 weeks of age (MGI Ref ID J:98073)
- obese
- postnatal growth retardation
- craniofacial phenotype
- abnormal nasal bone morphology
- main cause of craniofacial defects (MGI Ref ID J:98073)
- abnormal snout morphology
- short snout
- short, broad snouts seen in about 18% of animals (MGI Ref ID J:98073)
- skeleton phenotype
- abnormal nasal bone morphology
- main cause of craniofacial defects (MGI Ref ID J:98073)
- behavior/neurological phenotype
- increased vertical activity
- in an open field, mice rear more than wild-type mice (MGI Ref ID J:125089)
- seizures
- 2% of mice display seizures after the age of 4 months (MGI Ref ID J:125089)
- nervous system phenotype
- abnormal brain wave pattern
- video electroencephalogram indicates abnormal wake and sleep background with frequent epileptiform discharges despite the lack of electographic seizures (MGI Ref ID J:125089)
- seizures
- 2% of mice display seizures after the age of 4 months (MGI Ref ID J:125089)
Rai1tm1Jrl/Rai1tm1Jrl
involves: 129S/SvEvBrd * C57BL/6
- mortality/aging
- decreased survivor rate
- 1 mouse survived past 3 months (MGI Ref ID J:98073)
- partial embryonic lethality between implantation and somite formation
- partial lethality throughout fetal growth and development
- partial postnatal lethality
- growth/size phenotype
- postnatal growth retardation
- grossly normal at birth but severely growth retarded thereafter (MGI Ref ID J:98073)
- craniofacial phenotype
- abnormal nasal bone morphology
- sometimes curved to right or left (MGI Ref ID J:98073)
- abnormal snout morphology
- lateral bending of snout with and without misalignment of incisors (MGI Ref ID J:98073)
- short snout (MGI Ref ID J:98073)
- malocclusion
- sometimes upper and lower incisors are misaligned (MGI Ref ID J:98073)
- skeleton phenotype
- abnormal axial skeleton morphology (MGI Ref ID J:98073)
- abnormal cervical vertebrae morphology
- fusion of atlas and odontoid process
- odontoid process fused to atlas (MGI Ref ID J:98073)
- abnormal nasal bone morphology
- sometimes curved to right or left (MGI Ref ID J:98073)
- abnormal rib development
- 13th rib is thinner than normal and fails to articulate with vertebral body (MGI Ref ID J:98073)
- abnormal thoracic vertebrae morphology
- abnormal vertebral arch development
- kyphosis
- 10% of mice over 4 months of age display kyphosis (MGI Ref ID J:125089)
- malocclusion
- sometimes upper and lower incisors are misaligned (MGI Ref ID J:98073)
- abnormal thyroid cartilage morphology
- hypoplastic thyroid bones with central elements unformed (MGI Ref ID J:98073)
- polyphalangy
- extra cartilage seen in digit 5 (MGI Ref ID J:98073)
- limbs/digits/tail phenotype
- polyphalangy
- extra cartilage seen in digit 5 (MGI Ref ID J:98073)
- respiratory system phenotype
- abnormal thyroid cartilage morphology
- hypoplastic thyroid bones with central elements unformed (MGI Ref ID J:98073)
- behavior/neurological phenotype
- abnormal contextual conditioning behavior
- mice display defective context-dependent learning relative to wild-type mice (MGI Ref ID J:125089)
- abnormal cued conditioning behavior
- mice display defective cued (tone) conditioned learning relative to wild-type mice (MGI Ref ID J:125089)
- impaired coordination
- when placed on a vertical pole, mice fall off more frequently and more readily as compared to wild-type mice (MGI Ref ID J:125089)
- in a wire suspension test, mice fall off after 30 seconds compared to 60 seconds for heterozygotes (MGI Ref ID J:125089)
- when placed on a thin rod, mice fall off after 11 seconds compared to 60 seconds for wild-type mice (MGI Ref ID J:125089)
- increased anxiety-related response
- in a light-dark test, mice display increased latency to enter the light relative to wild-type mice (MGI Ref ID J:125089)
- limb grasping
- when suspended by their tails, mice display hindlimb, and occasionally hind- and forelimb, clasping even after three months of age whereas wild-type mice hold their legs apart (MGI Ref ID J:125089)
- seizures
- tonic-clonic seizures (MGI Ref ID J:125089)
- nervous system phenotype
- abnormal brain wave pattern
- seizures
- tonic-clonic seizures (MGI Ref ID J:125089)
This mouse can be used to support research in many areas including:
Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)
incomplete
Perinatal Lethality
Homozygous
Skeletal Defects
polydactyly
Diabetes and Obesity Research
Obesity Without Diabetes
Research Tools
lacZ Expression
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Rai1tm1Jrl | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, James R Lupski | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Rai1-; | ||
| Mutation Made By | James Lupski, Baylor College of Medicine | ||
| Strain of Origin | 129S/SvEvBrd | ||
| ES Cell Line Strain | 129 | ||
| Site of Expression | Heterozygous embryos show differential tissue expression of lacZ during development, mimicking the expression pattern of Rai1. | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | An approximately 4.0 kb of the coding region in exon 2 was replaced by an intra-ribosomal entry site IRES-lacZ-pA cassette followed by a loxP flanked PGKneobpA cassette. RT-PCR indicated that only sequence 5' of the deleted region was present in transcripts. This truncation eliminates all nuclear localization regions and the PHD domain. [MGI Ref ID J:98073] | ||
| Gene Symbol and Name | Rai1, retinoic acid induced 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | Gt1; SMCR; SMS; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Rai1tm1Jrl,SEPARATED MELT
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Bi W; Ohyama T; Nakamura H; Yan J; Visvanathan J; Justice MJ; Lupski JR. 2005. Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome. Hum Mol Genet 14(8):983-95. [PubMed: 15746153] [MGI Ref ID J:98073]
Additional References
Rai1tm1Jrl relatedBi W; Yan J; Shi X; Yuva-Paylor LA; Antalffy BA; Goldman A; Yoo JW; Noebels JL; Armstrong DL; Paylor R; Lupski JR. 2007. Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes. Hum Mol Genet 16(15):1802-13. [PubMed: 17517686] [MGI Ref ID J:125089]
Burns B; Schmidt K; Williams SR; Kim S; Girirajan S; Elsea SH. 2010. Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome. Hum Mol Genet 19(20):4026-42. [PubMed: 20663924] [MGI Ref ID J:164451]
Lacaria M; Saha P; Potocki L; Bi W; Yan J; Girirajan S; Burns B; Elsea S; Walz K; Chan L; Lupski JR; Gu W. 2012. A Duplication CNV That Conveys Traits Reciprocal to Metabolic Syndrome and Protects against Diet-Induced Obesity in Mice and Men. PLoS Genet 8(5):e1002713. [PubMed: 22654670] [MGI Ref ID J:185193]
Ricard G; Molina J; Chrast J; Gu W; Gheldof N; Pradervand S; Schutz F; Young JI; Lupski JR; Reymond A; Walz K. 2010. Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models. PLoS Biol 8(11):e1000543. [PubMed: 21124890] [MGI Ref ID J:170239]
Walz K; Paylor R; Yan J; Bi W; Lupski JR. 2006. Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2). J Clin Invest 116(11):3035-41. [PubMed: 17024248] [MGI Ref ID J:114996]
Yan J; Bi W; Lupski JR. 2007. Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. Am J Hum Genet 80(3):518-25. [PubMed: 17273973] [MGI Ref ID J:125240]
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 When maintaining a live colony, heterozygous mice are bred to wildtype siblings (or to Stock No. 000058, albino C57BL/6J). The vast majority of homozygotes die during development or before weaning age. As the background is C57BL/6 albino, mice are white.
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* $2250.00 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* $2925.00 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.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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The Jackson Laboratory's Genotype Promise
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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For Licensing and Use Restrictions view the link(s) below:
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Contact information
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