Overview

As deletions of the Snord116 cluster are associated with Prader-Willi syndrome (PWS), mice carrying the 2-loxP (floxed) allele may be useful in generating conditional mutations for studying the role of Snord116 in growth and feeding regulation, mechanisms of obesity, and pathophysiology of Prader-Willi syndrome. Of note, mice harboring a deletion of the Snord116 cluster are also available (see Stock No. 008149).

Donating Investigator

Dr. Uta Francke, Stanford University School of Medicine

Genetic overview

Genetic Background	Generation

Snord116^tm1Uta

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Snord116	small nucleolar RNA, C/D box 116 cluster

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Research Applications

Research Tools
Developmental Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this 2-loxP (floxed) allele are viable and fertile, with loxP sites flanking the Snord116 small nucleolar RNAs (snoRNAs) gene cluster. When bred to mice that express Cre recombinase, the resulting offspring will have this gene cluster deleted in the cre-expressing tissue(s). Because the Snord116 gene cluster is imprinted and only expressed from the paternal allele, breeding 2-loxP males with cre-expressing females may be required to generate deleted offspring with the knockout phenotype. The donating investigator reports that the distance between the two loxP sites (~140 kb) may reduce the recombination efficiency in somatic cells. As deletions of the Snord116 cluster are associated with Prader-Willi syndrome (PWS), mice carrying the 2-loxP (floxed) allele may be useful in generating conditional mutations for studying the role of Snord116 in growth and feeding regulation, mechanisms of obesity, and pathophysiology of Prader-Willi syndrome.

Of note, mice harboring a deletion of the Snord116 cluster are also available (see Stock No. 008149).

For example, when crossed to a strain expressing Cre recombinase in the female germline (see Stock No. 003651), this mutant mouse strain may be useful in studies of Prader-Willi syndrome.

Development

Two individual targeting vectors were used to place a loxP site (and an Frt1-flanked PGK-neo cassette) upstream, and a loxP site (and an Frt5-flanked puromycin resistance/TK cassette) downstream of the Snord116 cluster. The upstream targeting vector was transfected into C57BL/6-derived Bruce-4 embryonic stem (ES) cells, and correctly targeted ES cells were next transfected with the downstream targeting vector. Doubly targeted ES cells were then transiently transfected with an FLP expressing plasmid to remove the two selection cassettes. The resulting 2-loxP ES cells (with a single loxP site just upstream, and a single loxP site just downstream of the Snord116 cluster) were injected into recipient blastocysts. Chimeric males were bred to albino B6(Cg)-Tyr^c-2J/J (Stock No. 000058) females. The resulting females were then bred to C57BL/6 males (expressing cre in the female, but not male, germline (Zp3-cre; Stock No. 003651)). Offspring carrying the 2-loxP mutation (and not the Zp3-cre transgene) were selected and backcrossed to C57BL/6J inbred mice for 2 generations prior to arrival at The Jackson Laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Ding F; Li HH; Zhang S; Solomon NM; Camper SA; Cohen P; Francke U. 2008. SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice. PLoS One 3(3):e1709PubMed: 18320030 MGI: J:131427

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Genetics

Snord116^tm1Uta

Allele Symbol: Snord116^tm1Uta

Allele Name	targeted mutation 1, Uta Francke
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	2-lox; 2-loxp
Gene Symbol and Name	Snord116, small nucleolar RNA, C/D box 116 cluster
Gene Synonym(s)
Strain of Origin	B6.Cg-Thy1^a
Chromosome	7
Molecular Note	Two individual targeting vectors were used to place a loxP site (and an Frt1-flanked PGK-neo cassette) upstream, and a loxP site (and an Frt5-flanked puromycin resistance/TK cassette) downstream of the Snord116 cluster. The upstream targeting vector was transfected into C57BL/6-derived embryonic stem ES cells, and correctly targeted ES cells were next transfected with the downstream targeting vector. Doubly targeted ES cells were then transiently transfected with an FLP expressing plasmid to remove the two selection cassettes. The resulting 2-loxP ES cells (with a single loxP site just upstream, and a single loxP site just downstream of the Snord116 cluster.
Mutations Made By	Dr. Uta Francke, Stanford University School of Medicine

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Prader-Willi syndrome

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: transcriptional activation
  - Mutagenesis and Transgenesis
- Cell Biology Research
- Developmental Biology Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
Developmental Biology Research
- Imprinting
Neurobiology 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: Snord116^tm1Uta/Snord116⁺ Tg(Zp3-cre)93Knw/0
involves: C57BL/6J

adipose tissue phenotype

decreased percent body fat/body weight
- 5 month-old mutant males on regular chow diet show an insignificant trend (-3.6%) toward decreased body fat content while females show a significant decrease of 4.2% relative to wild-type; 9-month old animals on a regular chow diet significantly lower body fat content (-9% in mutant males, -5% in females)
- when fed a high-fat diet for 4 months, mutants carrying the paternally-inherited deletion allele have significantly lower body fat than wild-type animals (mutant males -6.9%, mutant females -7.2% lower than wild-type)
- y fat content (-9% in mutant males, -5% in females)

decreased total body fat amount
- on high-fat and normal chow diets, animals carrying the paternally-inherited deletion allele display decreased fat storage compared to wild-type animals

cellular phenotype

maternal imprinting
- the Snord116 cluster is imprinted and the maternal copy is silenced during oogenesis; only inheritance of the paternal allele with the Snord116 cluster deletion produces the growth deficiency and polyphagia phenotypes in mice
- Normal - when offspring have maternal inheritance of the deleted allele, they are normal in size and show normal lifespans

digestive/alimentary phenotype

small stomach
- stomachs in animals receiving paternally-inherited mutant allele are significantly smaller than in wild-type littermates; at P5 and 13, stomachs are 67 and 68% the size of wild-type

growth/size/body region phenotype

decreased body length
- at 5 months of age, body lengths of mutant males and females are shorter by around 4 and 3%, respectively, than wild-type mice (differences are statistically significant)

decreased susceptibility to diet-induced obesity
- when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males

postnatal growth retardation

slow postnatal weight gain
- at birth, pups with the paternally-inherited allele are indistinguishable from normal littermates, but beginning at P2, mutants fail to gain weight as effectively as littermates; by 3 weeks, mutant weights are 60% of wild-type male and female weights
- growth rates appear to normalize after weaning, but weight differences persist to maturity in both genders

homeostasis/metabolism phenotype

abnormal homeostasis
- show improved weight stability compared to wild-type)
- when mice are restricted to 80% of their normal food intake levels, wild-type mice gradually lose weight but animals carrying the paternally-inherited deletion allele are better at maintaining their weight (females are significantly better, but males also show improved weight stability compared to wild-type)

decreased circulating glucose level
- on a high-fat diet, males carrying the paternally-inherited deletion allele have lower resting blood glucose levels and display a smaller peak level after glucose injecion compared to wild-type males

decreased circulating insulin-like growth factor I level
- animals with paternally-inherited mutant allele have 39% of wild-type level at 4 weeks of age, and 57% of wild-type levels at 8 weeks

decreased susceptibility to diet-induced obesity
- when fed a high-fat diet for 4 months from 8 weeks of age, mutants carrying the paternally-inherited deletion gain less weight than wild-type littermates, with the differences more pronounced in males

increased circulating ghrelin level
- when allowed ad libitum food access, adult mice carrying the paternally-inherited deletion allele have ghrelin levels 2.3-fold higher than in wild-type animals

increased insulin sensitivity
- d insulin sensitivity
- on a normal diet, males carrying the paternally-inherited deletion have similar basal blood glucose levels to wild-type but display significantly increased response to insulin injection; mutant males fed a high-fat diet also display significantly increased insulin sensitivity

increased oxygen consumption
- mice carrying the paternally-inherited deletion allele have significantly rates of oxygen consumption

increased respiratory quotient
- mice carrying the paternally-inherited deletion allele exhibit a higher respiratory exchange ratio than wild-type mice

liver/biliary system phenotype

decreased liver weight
- at P5, liver weight is 72% of wild-type animals, and at p13, liver weight is only 56% of wild-type

small liver
- size is strikingly reduced in size upon examination at P5 and 13

mammalian phenotype

behavior/neurological phenotype
- Normal - unlike other mouse models of Prader-Willi syndrome, mutant pups carrying the paternally-inherited deletion show normal milk intake, righting ability, and muscle tone and strenght after birth and during early postnatal period

endocrine/exocrine gland phenotype
- Normal - morphology of pituitary gland in mutants is normal

mortality/aging
- Normal - almost all mutants with the paternally inherited deletion survive to adulthood and appear healthy at 18 months

reproductive system phenotype
- Normal - testis and ovary sizes of mutants carrying the paternally-inherited deletion are proportional to their body size, and histologically normal

nervous system phenotype

decreased brain weight
- at P5 and 13, brain weight is only slight decreased (95% and 92%, respectively, of wild-type brain weight)

reproductive system phenotype

delayed vaginal opening
- in mutant females with the paternally-inherited deletion, vaginal opening is delayed by 3.7 days

behavior/neurological phenotype

abnormal food intake
- d-type, indicating that mutants compensate for reduced 'day-time' intake by increasing intake during dark-phase)
- when provided with a high-fat diet, both wild-type and mutant animals reduce their total food intake, but both mutant males and females have lower food intake during the 'day-time' phase relative to wild-type animals (total energy intake is similar to wild-type, indicating that mutants compensate for reduced 'day-time' intake by increasing intake during dark-phase)

abnormal motor learning
- in accelerating rotarod trials at 2 and 5 months of age, mice carrying the paternally-inherited deletion display essentially flat learning curves (little improvement) over a 6-day training period, whereas control animals display significant improvements

increased anxiety-related response
- 3-4 month old mice with the paternally-inherited deletion exhibit increased anxiety-relatted behavior in elevated plus-maze tests (more entries into and time spent in closed arms of maze relative to wild-type mice)

polyphagia
- at 10 months, males and females carrying the paternally-inherited deletion allele display significant hyperphagia with daily food intake increased by 31 and 29% respectively compared to wild-type animals
- at 6 months of age, both males and females carrying the paternally-inherited deletion allele show increases in daily food intake normalized to body weight (22% or 32%, respectively; at 3 months, males show significant hyperphagia relative to wild-type males, but to a lesser degree than at 6 months, while in females carrying the paternally-inherited deletion allele, daily food intake increases do not reach significance
- es, but to a lesser degree than at 6 months, while in females carrying the paternally-inherited deletion allele, daily food intake increases do not reach significance

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

Genotype: Snord116^tm1Uta/Snord116^tm1Uta
involves: C57BL/6J

normal phenotype

no abnormal phenotype detected
- Normal - homozygous mice are viable and fertile

References

Ding F; Li HH; Zhang S; Solomon NM; Camper SA; Cohen P; Francke U. 2008. SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice. PLoS One 3(3):e1709PubMed: 18320030 MGI: J:131427

Additional - Snord116^tm1Uta related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Snord116
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together. As imprinting of the endogenous gene is determined via paternal inheritance, paternal transmission of the mutant allele may be required.
- Additional Breeding and Husbandry Support
Citation
When using the B6(Cg)-Snord116^tm1Uta/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008118 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Snord116<tm1Uta>

Related Products and Services

Frozen Mouse Embryo	B6(Cg)-Snord116<tm1Uta>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6(Cg)-Snord116<tm1Uta>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6(Cg)-Snord116<tm1Uta>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6(Cg)-Snord116<tm1Uta>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Snord116tm1Uta

Allele Symbol: Snord116tm1Uta

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Snord116tm1Uta/Snord116+ Tg(Zp3-cre)93Knw/0involves: C57BL/6J

adipose tissue phenotype

cellular phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

mammalian phenotype

nervous system phenotype

reproductive system phenotype

behavior/neurological phenotype

Genotype: Snord116tm1Uta/Snord116tm1Utainvolves: C57BL/6J

normal phenotype

References

Additional - Snord116tm1Uta related

Genotyping Protocols

Breeding Considerations

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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Snord116^tm1Uta

Allele Symbol: Snord116^tm1Uta

Genotype: Snord116^tm1Uta/Snord116⁺ Tg(Zp3-cre)93Knw/0
involves: C57BL/6J

Genotype: Snord116^tm1Uta/Snord116^tm1Uta
involves: C57BL/6J

Additional - Snord116^tm1Uta related