Description

Strain Information

Former Names C57BL/6-Snord116tm1Uta/J    (Changed: 19-MAY-08 ) Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N3+F1 (12-MAY-08)   Donating Investigator Dr. Uta Francke,   Stanford University School of Medicine

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 Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Snord116

008149

B6(Cg)-Snord116tm1.1Uta/J

View Strains carrying other alleles of Snord116     (1 strain)

Additional Web Information

Cre-lox Systems

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Snord116^tm1Uta/Snord116^tm1Uta

        involves: C57BL/6J

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:131427)
  • homozygous mice are viable and fertile

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Snord116^tm1Uta/Snord116⁺ Tg(Zp3-cre)93Knw/0

        involves: C57BL/6J   (conditional)

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:131427)
  • almost all mutants with the paternally inherited deletion survive to adulthood and appear healthy at 18 months
• growth/size phenotype
• decreased body length (MGI Ref ID J:131427)
  • 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)
• increased resistance to diet-induced obesity (MGI Ref ID J:131427)
  • 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 (MGI Ref ID J:131427)
• postnatal slow weight gain (MGI Ref ID J:131427)
  • 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
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:131427)
  • 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
• abnormal food intake (MGI Ref ID J:131427)
  • 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)
• polyphagia (MGI Ref ID J:131427)
  • 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
  • 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
• abnormal motor learning (MGI Ref ID J:131427)
  • 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 (MGI Ref ID J:131427)
  • 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)
• nervous system phenotype
• decreased brain weight (MGI Ref ID J:131427)
  • at P5 and 13, brain weight is only slight decreased (95% and 92%, respectively, of wild-type brain weight)
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:131427)
  • testis and ovary sizes of mutants carrying the paternally-inherited deletion are proportional to their body size, and histologically normal
• delayed vaginal opening (MGI Ref ID J:131427)
  • in mutant females with the paternally-inherited deletion, vaginal opening is delayed by 3.7 days
• endocrine/exocrine gland phenotype
• *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:131427)
  • morphology of pituitary gland in mutants is normal
• homeostasis/metabolism phenotype
• abnormal homeostasis (MGI Ref ID J:131427)
  • 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)
• abnormal hormone level (MGI Ref ID J:131427)
  • 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
• decreased circulating insulin-like growth factor I level (MGI Ref ID J:131427)
  • 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
• abnormal respiratory quotient (MGI Ref ID J:131427)
  • mice carrying the paternally-inherited deletion allele exhibit a higher respiratory exchange ratio than wild-type mice
• decreased circulating glucose level (MGI Ref ID J:131427)
  • 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
• increased insulin sensitivity (MGI Ref ID J:131427)
  • 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 (MGI Ref ID J:131427)
  • mice carrying the paternally-inherited deletion allele have significantly rates of oxygen consumption
• increased resistance to diet-induced obesity (MGI Ref ID J:131427)
  • 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
• adipose tissue phenotype
• decreased adipose tissue amount (MGI Ref ID J:131427)
  • on high-fat and normal chow diets, animals carrying the paternally-inherited deletion allele display decreased fat storage compared to wild-type animals
• decreased percent body fat (MGI Ref ID J:131427)
  • 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)
  • 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)
• digestive/alimentary phenotype
• small stomach (MGI Ref ID J:131427)
  • 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
• liver/biliary system phenotype
• small liver (MGI Ref ID J:131427)
  • size is strikingly reduced in size upon examination at P5 and 13
• decreased liver weight (MGI Ref ID J:131427)
  • at P5, liver weight is 72% of wild-type animals, and at p13, liver weight is only 56% of wild-type
• cellular phenotype
• maternal imprinting (MGI Ref ID J:131427)
  • 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
  • when offspring have maternal inheritance of the deleted allele, they are normal in size and show normal lifespans

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System (loxP-flanked Sequences)

Research Tools
Cell Biology Research
Cre-lox System (loxP-flanked Sequences)
Developmental Biology Research (Cre-lox System)
Genetics Research (Mutagenesis and Transgenesis: transcriptional activation)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Snord116tm1Uta
Allele Name		targeted mutation 1, Uta Francke
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		2-lox; 2-loxp;
Mutation Made By		Dr. Uta Francke,   Stanford University School of Medicine
Strain of Origin		C57BL/6
ES Cell Line Name		Bruce 4
ES Cell Line Strain		C57BL/6
Gene Symbol and Name		Snord116, small nucleolar RNA, C/D box 116
Chromosome		7
Gene Common Name(s)		Prader-Willi chromosome region 1 homolog (human); Pwcr1; snoRNA MBII-85;
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. [MGI Ref ID J:131427]

Genotyping

Genotyping Information

Genotyping Protocols

Snord116^tm1Uta, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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):e1709. [PubMed: 18320030]  [MGI Ref ID J:131427]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	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.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
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phone:	207-288-6470
fax:	207-288-6655

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