Overview

Also Known As:Rai1-flox (Rai1^flox)

The Rai1^flox allele has loxP sites flanking exon 3 of the retinoic acid induced 1 gene. Removal of the floxed sequence creates a null allele. These mice may be useful in studying circuit assembly and neuronal communication in human disorders such as Smith-Magenis syndrome(SMS).

Donating Investigator

Liqun Luo, Stanford University

Genetic overview

Genetic Background	Generation

Rai1^tm2.1Luo

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed))	Rai1	retinoic acid induced 1

View Genetics

Research Applications

Diabetes and Obesity Research
Research Tools
Neurobiology Research
Cell Biology Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Haploinsufficiency of retinoic acid induced 1 (RAI1) in humans causes Smith-Magenis syndrome (SMS), which is associated with diverse neurodevelopmental and behavioral symptoms as well as obesity. RAI1 encodes a nuclear protein with emerging functions in the expression of genes involved in circuit assembly and neuronal communication.

The Rai1^flox allele has loxP sites flanking exon 3 of the retinoic acid induced 1 gene. Mice homozygous for this floxed allele are viable and fertile with no reported abnormalities. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed region (encoding amino acid 1-1837) deleted in cre-expressing tissues; creating a knock-out allele (Rai1^Δ).

For example, when bred to mice with Cre-expression throughout the central and peripheral nervous system (Nestin-Cre; Stock No. 003771), the resulting Nestin^Cre;Rai1^CKO homozygotes have pan-neural loss of Rai1 and exhibit three major characteristics of SMS - deficits in body weight homeostasis, motor function and associative learning and memory. They are smaller than control littermates prior to weaning and show prominent hindlimb clasping. More than 80% die by 25 weeks of age. Females (but not males) show obesity beginning ~5 weeks of age.

Furthermore, individual aspects of these three major SMS phenotypes may be observed by crossing Rai1^flox to different cre-expressing mice.

Breeding to Gad2-IRES-Cre mice (Stock No. 010802) results in Rai1 knock-out in most GABAergic inhibitory neurons. Those Gad2^Cre;Rai1^CKO mice show learning deficits, but no motor function abnormalities, obesity or early lethality.

When bred to Vglut2-ires-cre mice (Stock No. 016963), the resulting Vglut2^Cre;Rai1^Tag mice have Rai1 knock-out in subcortical excitatory neurons - leading to increased body weight, poor motor function and learning deficits, with no early lethality. In addition, Rai1 knock-out specifically in neurons of the paraventricular nucleus of hypothalamus (PVH ; via breeding to Sim1-cre [see Stock No. 006395]) or ventromedial nucleus of hypothalamus (VMH ; via breeding to Sf1-Cre [Stock No. 012462]) both contributed to the obesity phenotype observed in Vglut2^Cre;Rai1^CKO mice.

No SMS-like characteristics were observed for mice with Rai1 knock-out in astrocytes and subsets of adult neural progenitors (via breeding to Gfap-Cre73.12 ; Stock No. 012886) or with Rai1 knock-out in cortical and hippocampal excitatory neurons and glia (via breeding to Emx1-IRES-Cre; Stock No. 005628).

Development

The Rai1^flox (floxed exon 3) allele was created by Dr. Liqun Luo (Stanford University). First, a targeting vector was designed to insert a frt5-flanked neo cassette (frt5-pSV40-Neo-pA-frt5) and a loxP site upstream of exon 3, and a loxP downstream of exon 3 of the retinoic acid induced 1 gene (Rai1) on chromosome 11. The targeting vector was electroporated into 129S1/Sv-derived embryonic stem (ES) cells. Chimeric males were mated with Flp-transgenic females (undisclosed genetic background) for germline deletion of the neo cassette. The resulting Rai1^flox mice were backcrossed to C57BL/6J wildtype mice for at least four generations (and the Flp-expressing transgene was removed) prior to sending males with black coat color to The Jackson Laboratory Repository in 2017. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Of note, the donating investigator reports that, at least once during backcrossing, a heterozygous female was bred to a C57BL/6J inbred male (thus the Y chromosome of the congenic strain is of C57BL/6J origin).

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Huang WH; Guenthner CJ; Xu J; Nguyen T; Schwarz LA; Wilkinson AW; Gozani O; Chang HY; Shamloo M; Luo L. 2016. Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron 92(2):392-406PubMed: 27693255 MGI: J:237687

View All References

Genetics

Rai1^tm2.1Luo

Allele Symbol: Rai1^tm2.1Luo

Allele Name	targeted mutation 2.1, Liqun Luo
Allele Type	Targeted (Conditional ready (e.g. floxed))
Allele Synonym(s)	targeted mutation 2.1, Liqun Luo; Rai1^tm2.1Luo
Gene Symbol and Name	Rai1, retinoic acid induced 1
Gene Synonym(s)	Gt1; SMS; SMCR
Strain of Origin	129S1/Sv
Chromosome	11
Molecular Note	A targeting vector was designed to insert a FRT5-flanked neo cassette (frt5-pSV40-Neo-pA-frt5) and a loxP site upstream of exon 3, and a loxP downstream of exon 3. Flp-mediated recombination removed the FRT5-flanked neo cassette.

Disease/Phenotype

Disease Terms

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

Research Areas By Phenotype

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

Diabetes and Obesity Research
- Obesity Without Diabetes
  - females
Research Tools
- Cell Biology Research
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
- Reproductive Biology Research
  - Cre-lox System
- Diabetes and Obesity Research
  - loxP
- Cardiovascular Research
  - Cre-lox System
- Genetics Research
  - Mutagenesis and Transgenesis: transcriptional activation
  - Mutagenesis and Transgenesis: Cre-lox System
- Neurobiology Research
- Cancer Research
  - Cre-lox System
Neurobiology Research
- Behavioral and Learning Defects
- Cre-lox System
  - loxP-flanked Sequences
- Metabolic Defects
- Neuromuscular defects
Cell Biology Research
- Transcriptional Regulation
- Signal Transduction
Cancer Research
- Cre-lox System
  - loxP-flanked Sequences

Mammalian Phenotype Terms by Genotype

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

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Nes-cre)1Kln/?
either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

behavior/neurological phenotype

abnormal associative learning
- decreased freezing behavior after repeated tone-shock pairings during training

abnormal spatial working memory
- reduced tendency to explore new arm in Y maze

impaired contextual conditioning behavior
- decreased freezing behavior in contextual recall in trace fear-conditioning task

impaired coordination
- decreased latency to fall in wire hang test
- in pole test males slip from pole or climb down in a slow and uncoordinated fashion

impaired cued conditioning behavior
- decreased freezing behavior in cued recall

limb grasping
- hindlimb clasping

mammalian phenotype

behavior/neurological phenotype
- Normal - males have normal hearing and pain responses
- Normal - males perform similar to controls in assays for gait, velocity, vertical activity, anxiety, sociability and cognition

mortality/aging

premature death
- more than 80% of mice die before 25 weeks of age

skeleton phenotype

kyphosis
- kyphosis in 10% of mice that die before 10 weeks of age

growth/size/body region phenotype

decreased body size
- mice are smaller than littermates prior to weaning

obese
- at 20 weeks female mice are 101% heavier than controls
- female mice become overweight beginning at 5 weeks of age

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Nes-cre)1Kln/?
either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

behavior/neurological phenotype

impaired coordination
- males exhibit a decreased latency to fall in wire hang test

growth/size/body region phenotype

obese
- at 20 weeks female mice are 35% heavier than controls
- female mice become overweight beginning at 7 weeks of age

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Slc17a6^tm2(cre)Lowl/?
either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

abnormal associative learning

impaired contextual conditioning behavior
- decreased freezing behavior in contextual recall in trace fear-conditioning task

impaired coordination
- increased latency to fall in wire hang test
- increased time required to descend in pole test

impaired cued conditioning behavior
- decreased freezing behavior in cued recall

growth/size/body region phenotype

obese
- males and females become obese at 9 and 7 weeks, respectively and are 56% (males) and 116% (females) heavier than controls at 20 weeks

Genotype: Rai1^tm2.1Luo/Rai1⁺ Slc17a6^tm2(cre)Lowl/?
either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

impaired coordination
- increased latency to fall in wire hang test

growth/size/body region phenotype

increased body weight
- males and females exhibit 16% and 29% (respectively ) increased body weight as compared to controls

Genotype: Gad2^tm2(cre)Zjh/? Rai1^tm2.1Luo/Rai1^tm2.1Luo
either: (involves: 129S1/Sv * 129S4/SvJae * C57BL/6) or (involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

abnormal associative learning

impaired contextual conditioning behavior
- decreased freezing behavior in contextual memory recall

impaired cued conditioning behavior
- decreased freezing behavior in cued recall

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Sim1-cre)1Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

adipose tissue phenotype

increased body fat mass

increased total fat pad weight
- increased fat pad weight: gonadal, subcutaneous, retroperitoneal, mesenteric and BAT

mammalian phenotype

behavior/neurological phenotype
- Normal - males exhibit no motor weakness in wire hang test

behavior/neurological phenotype

hypoactivity
- decreased horizontal locomotor activity

polyphagia
- hyperphagic with a 47% increase in average daily food intake

growth/size/body region phenotype

increased body fat mass

increased lean body mass

obese
- mice are 57% heavier than controls at 20 weeks of age

homeostasis/metabolism phenotype

increased cholesterol level

increased circulating HDL cholesterol level

increased circulating LDL cholesterol level

increased circulating VLDL cholesterol level

increased triglyceride level

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Sim1-cre)1Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

increased body weight
- females are 12.7% heavier than controls at 20 weeks of age

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Nr5a1-cre)7Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

increased body weight
- females are 27% heavier than controls at 20 weeks of age

mammalian phenotype

behavior/neurological phenotype
- Normal - males exhibit no motor weakness in wire hang test

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Nr5a1-cre)7Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

increased body weight
- females are 27% heavier than controls at 20 weeks of age

Genotype: Emx1^tm1(cre)Krj/? Rai1^tm2.1Luo/Rai1^tm2.1Luo
either: (involves: 129S1/Sv * 129S2/SvPas * C57BL/6) or (involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6)

normal phenotype

no abnormal phenotype detected
- mice do not exhibit differences in behavior, motor function or body weight from controls

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Gfap-cre)73.12Mvs/?
either: (involves: 129S1/Sv * BALB/c * C57BL/6 * C57BL/6NHsd) or (involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6NHsd)

normal phenotype

no abnormal phenotype detected
- mice do not exhibit differences in behavior, motor function or body weight

References

Huang WH; Guenthner CJ; Xu J; Nguyen T; Schwarz LA; Wilkinson AW; Gozani O; Chang HY; Shamloo M; Luo L. 2016. Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome. Neuron 92(2):392-406PubMed: 27693255 MGI: J:237687

Additional - Rai1^tm2.1Luo related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Rai1-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for the Rai1^flox allele are viable and fertile with no reported gross physical or behavioral abnormalities.

When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
Citation
When using the Rai1-flox (Rai1^flox) mouse strain in a publication, please cite the originating article(s) and include JAX stock #029103 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Rai1<tm2.1Luo>

Related Products and Services

Frozen Mouse Embryo	B6.129S1(Cg)-Rai1<tm2.1Luo>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S1(Cg)-Rai1<tm2.1Luo>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S1(Cg)-Rai1<tm2.1Luo>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S1(Cg)-Rai1<tm2.1Luo>/J Frozen Embryo	$3373.50

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Also Known As:Rai1-flox (Rai1flox)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Rai1tm2.1Luo

Allele Symbol: Rai1tm2.1Luo

Disease Terms

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).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Rai1tm2.1Luo/Rai1tm2.1Luo Tg(Nes-cre)1Kln/?either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

behavior/neurological phenotype

mammalian phenotype

mortality/aging

skeleton phenotype

growth/size/body region phenotype

Genotype: Rai1tm2.1Luo/Rai1+ Tg(Nes-cre)1Kln/?either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Rai1tm2.1Luo/Rai1tm2.1Luo Slc17a6tm2(cre)Lowl/?either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Rai1tm2.1Luo/Rai1+ Slc17a6tm2(cre)Lowl/?either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Gad2tm2(cre)Zjh/? Rai1tm2.1Luo/Rai1tm2.1Luoeither: (involves: 129S1/Sv * 129S4/SvJae * C57BL/6) or (involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6)

behavior/neurological phenotype

Genotype: Rai1tm2.1Luo/Rai1tm2.1Luo Tg(Sim1-cre)1Lowl/?either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

adipose tissue phenotype

mammalian phenotype

behavior/neurological phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Rai1tm2.1Luo/Rai1+ Tg(Sim1-cre)1Lowl/?either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

Genotype: Rai1tm2.1Luo/Rai1tm2.1Luo Tg(Nr5a1-cre)7Lowl/?either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

mammalian phenotype

Genotype: Rai1tm2.1Luo/Rai1+ Tg(Nr5a1-cre)7Lowl/?either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

growth/size/body region phenotype

Genotype: Emx1tm1(cre)Krj/? Rai1tm2.1Luo/Rai1tm2.1Luoeither: (involves: 129S1/Sv * 129S2/SvPas * C57BL/6) or (involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6)

normal phenotype

Genotype: Rai1tm2.1Luo/Rai1tm2.1Luo Tg(Gfap-cre)73.12Mvs/?either: (involves: 129S1/Sv * BALB/c * C57BL/6 * C57BL/6NHsd) or (involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6NHsd)

normal phenotype

References

Additional - Rai1tm2.1Luo related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Rai1-flox (Rai1^flox)

Rai1^tm2.1Luo

Allele Symbol: Rai1^tm2.1Luo

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Nes-cre)1Kln/?
either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Nes-cre)1Kln/?
either: (involves: 129S1/Sv * C57BL/6 * SJL) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL)

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Slc17a6^tm2(cre)Lowl/?
either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

Genotype: Rai1^tm2.1Luo/Rai1⁺ Slc17a6^tm2(cre)Lowl/?
either: (involves: 129S1/Sv * 129S6/SvEvTac * C57BL/6) or (involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6)

Genotype: Gad2^tm2(cre)Zjh/? Rai1^tm2.1Luo/Rai1^tm2.1Luo
either: (involves: 129S1/Sv * 129S4/SvJae * C57BL/6) or (involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6)

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Sim1-cre)1Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Sim1-cre)1Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Nr5a1-cre)7Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

Genotype: Rai1^tm2.1Luo/Rai1⁺ Tg(Nr5a1-cre)7Lowl/?
either: (involves: 129S1/Sv * C57BL/6 * FVB) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB)

Genotype: Emx1^tm1(cre)Krj/? Rai1^tm2.1Luo/Rai1^tm2.1Luo
either: (involves: 129S1/Sv * 129S2/SvPas * C57BL/6) or (involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6)

Genotype: Rai1^tm2.1Luo/Rai1^tm2.1Luo Tg(Gfap-cre)73.12Mvs/?
either: (involves: 129S1/Sv * BALB/c * C57BL/6 * C57BL/6NHsd) or (involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6NHsd)

Additional - Rai1^tm2.1Luo related