Description

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. Mating System See Colony Maintenance under the Health & husbandry tab         (Female x Male)   26-OCT-11 Species laboratory mouse   Donating Investigator James Resnick,   University of Florida

Description
When females heterozygous for the PWS-IC^del mutation are bred with wildtype males, the resulting offspring are viable and fertile as adults. In contrast, paternal transmission of the PWS-IC^del mutation results in neonatal lethality between 1-7 days of age (failure to thrive) due to imprinting defects. Most of these pups will die within 48 hours, however, a few live to 7 days. Pups are underweight, unable to support themselves, dehydrated and weak. Although capable of nursing, little milk is observed in their stomachs and they develop low blood glucose levels. Of note, removing all but one wildtype littermate improves mutant mouse survivability. In addition, mutant mouse viability may be greatly improved by outcrossing to FVB/NJ females. These PWS-IC^del mutant mice may be useful in studying the Prader Willi syndrome imprinting center.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 35 kB of genomic DNA replacing 16 kB of upstream sequence including the putative imprinting center (IC) and exons 1 through 6. The construct was electroporated into 129-derived J4(XO) embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The donating investigator reports that this strain is derived from neomycin resistant isolate 328. Initially, chimeric males were crossed to C57BL/6J females, however paternal transmission of the allele results in perinatal lethality. The donating investigator maintained these PWS-IC^del mutant mice by breeding heterozygous females to C57BL/6J males for at least 19 generations prior to sending to The Jackson Laboratory Repository. Upon arrival, females heterozygous for the PWS-IC^del mutation were bred with C57BL/6J inbred males (Stock No. 000664) to establish the colony.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Snrpn

018395

B6.129S1-Snrpntm2.1Kaj/J

View Strains carrying other alleles of Snrpn     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- 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

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Autism   (SNRPN)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Snrpn^tm2Cbr/Snrpn⁺

        either: B6.Cg-Snrpn^tm2Cbr or (involves: 129S1/Sv * C57BL/6J * DBA/2J)

• mortality/aging
• complete postnatal lethality
  • all pups die within 7 days of birth   (MGI Ref ID J:94414)
  • survival is impaired compared to heterozygous pups from crosses of heterozygous males to wild-type females of the 129S1/Sv, BALB/c, C3H/HeJ, or FVB/NJ strains   (MGI Ref ID J:94414)
• cellular phenotype
• maternal imprinting   (MGI Ref ID J:94414)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Snrpn^tm2Cbr/Snrpn⁺

        involves: 129S1/Sv * C57BL/6

• mortality/aging
• complete postnatal lethality
  • 72% of heterozygotes die within 48 hours of birth with none surviving past 7 days of age   (MGI Ref ID J:47318)
• partial postnatal lethality
  • less than 5% of mice heterozygous for the paternally inherited deletion allele alone survive to weaning   (MGI Ref ID J:105412)
• behavior/neurological phenotype
• abnormal stationary movement
  • heterozygotes are unable to support themselves on their hind feet and instead rest on their knees   (MGI Ref ID J:47318)
• abnormal suckling behavior
  • heterozygotes are capable of suckling but consistently have less milk in their stomachs compared to wild-type littermates   (MGI Ref ID J:47318)
• weakness
  • mice that survive past 2 days display weakness   (MGI Ref ID J:105412)
• growth/size phenotype
• decreased birth weight
  • on the day of birth heterozygotes appear normal but weigh about 20% less than wild-type littermates   (MGI Ref ID J:47318)
• postnatal growth retardation
  • mice that survive past 2 days fail to maintain normal growth rates   (MGI Ref ID J:47318)
• homeostasis/metabolism phenotype
• decreased circulating glucose level   (MGI Ref ID J:47318)
• dehydration
  • mice that survive past 2 days appear dehydrated   (MGI Ref ID J:47318)
• reproductive system phenotype
• *normal* reproductive system phenotype
  • no genital or gonadal hypoplasia is seen at birth   (MGI Ref ID J:47318)
• cellular phenotype
• maternal imprinting   (MGI Ref ID J:105412)
  • in J:47318 all heterozygotes carry a paternally inherited mutant allele   (MGI Ref ID J:47318)

Snrpn^tm2Cbr/Snrpn⁺

        either: (involves: 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * BALB/c * C57BL/6J) or (involves: 129S1/Sv * C3H/HeJ * C57BL/6J) or (involves: 129S1/Sv * C57BL/6J * FVB/NJ)

• mortality/aging
• complete postnatal lethality
  • most heterozygous pups die within 14 days of birth but with removal of all but 1 wild-type littermate some survive to adulthood and are fertile   (MGI Ref ID J:94414)
  • all heterozygous pups die within 7 days of birth when a heterozygous male on a 129S1/Sv background is crossed to a wild-type female of the C57BL/6J strain unlike the reciprocal cross where some heterozygous pups survive   (MGI Ref ID J:94414)
  • survival is improved compared to heterozygous pups from crosses of heterozygous males (on a C57BL/6J background) to wild-type females of the C57BL/6J or DBA/2J strains   (MGI Ref ID J:94414)
  • if the wild-type female crossed to a heterozygous male is an F1 cross of C57BL/6J and either C3H/HeJ, or FVB/NJ survival of heterozygous pups is impaired compared to crosses where the female is inbred C3H/HeJ, or FVB/NJ   (MGI Ref ID J:94414)
• growth/size phenotype
• decreased body size
  • as adults surviving pups are significantly smaller than wild-type littermates and never become obese   (MGI Ref ID J:94414)
• reproductive system phenotype
• *normal* reproductive system phenotype
  • survivng heterozygotes are fertile   (MGI Ref ID J:94414)
• cellular phenotype
• maternal imprinting   (MGI Ref ID J:94414)

View Research Applications

Research Applications

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

Developmental Biology Research
Imprinting
Perinatal Lethality

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Snrpntm2Cbr
Allele Name		targeted mutation 2, Camilynn I Brannan
Allele Type		Targeted (knock-out)
Common Name(s)		IC deletion; PWS-IC deletion; PWS-ICdel35kb; PWS-ICdel; deltaPWS-IC;
Mutation Made By		Dr. Camilynn Brannan,   Univ of Florida College of Medicine
Strain of Origin		129S/Sv
Gene Symbol and Name		Snrpn, small nuclear ribonucleoprotein N
Chromosome		7
Gene Common Name(s)		2410045I01Rik; FE 294; FE 294 psi; FE294; FE294 psi; HCERN3; MGC:18604; MGC:30325; PWCR; Peg4; Pwcr1; RIKEN cDNA 2410045I01 gene; RT-LI; SM-D; SMN; SNRNP-N; SNURF-SNRPN; sm-N;
General Note		ES cell line = CJ7 or J4. In J:47318 CJ7 male ES cells were used. All offspring generated from crosses of these chimeras to C57BL/6 females died by postnatal day 7. In J:61887 the same targeting vector was used in CJ7 (male) and J4 (female, XO) ES cells. It is unclear which of these targeting events was used to generate the line of mice used in subsequent papers as both parental inheritence of the allele and strain background influence the survival of offspring.
Molecular Note		A PGK-neomycin resistance cassette replaced 35kb of sequence encompassing 16kb upstream of the gene and exons 1-6. The portion of the targeted locus including the neo gene and 5' sequences was amplified four fold in the targeted allele. Northern blot analysis of brain tissue using a cDNA probe for the gene did not detect any transcript in heterozygous mutant mice. [MGI Ref ID J:47318] [MGI Ref ID J:61887] [MGI Ref ID J:69578]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chamberlain SJ; Johnstone KA; DuBose AJ; Simon TA; Bartolomei MS; Resnick JL; Brannan CI. 2004. Evidence for genetic modifiers of postnatal lethality in PWS-IC deletion mice. Hum Mol Genet 13(23):2971-7. [PubMed: 15459179]  [MGI Ref ID J:94414]

Yang T; Adamson TE; Resnick JL; Leff S; Wevrick R; Francke U ; Jenkins NA ; Copeland NG ; Brannan CI. 1998. A mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet 19(1):25-31. [PubMed: 9590284]  [MGI Ref ID J:47318]

Additional References

Snrpn^tm2Cbr related

Bielinska B; Blaydes SM; Buiting K; Yang T; Krajewska-Walasek M; Horsthemke B; Brannan CI. 2000. De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch [see comments] Nat Genet 25(1):74-8. [PubMed: 10802660]  [MGI Ref ID J:61887]

Chamberlain SJ; Brannan CI. 2001. The prader-willi syndrome imprinting center activates the paternally expressed murine ube3a antisense transcript but represses paternal ube3a. Genomics 73(3):316-22. [PubMed: 11350123]  [MGI Ref ID J:69578]

Doe CM; Relkovic D; Garfield AS; Dalley JW; Theobald DE; Humby T; Wilkinson LS; Isles AR. 2009. Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour. Hum Mol Genet 18(12):2140-8. [PubMed: 19304781]  [MGI Ref ID J:148545]

Johnstone KA; DuBose AJ; Futtner CR; Elmore MD; Brannan CI; Resnick JL. 2006. A human imprinting centre demonstrates conserved acquisition but diverged maintenance of imprinting in a mouse model for Angelman syndrome imprinting defects. Hum Mol Genet 15(3):393-404. [PubMed: 16368707]  [MGI Ref ID J:105412]

Leung KN; Vallero RO; DuBose AJ; Resnick JL; LaSalle JM. 2009. Imprinting regulates mammalian snoRNA-encoding chromatin decondensation and neuronal nucleolar size. Hum Mol Genet 18(22):4227-38. [PubMed: 19656775]  [MGI Ref ID J:153722]

Peery EG; Elmore MD; Resnick JL; Brannan CI; Johnstone KA. 2007. A targeted deletion upstream of Snrpn does not result in an imprinting defect. Mamm Genome 18(4):255-62. [PubMed: 17514346]  [MGI Ref ID J:121982]

Peters J; Beechey C. 2004. Identification and characterisation of imprinted genes in the mouse. Brief Funct Genomic Proteomic 2(4):320-33. [PubMed: 15163367]  [MGI Ref ID J:187438]

Relkovic D; Doe CM; Humby T; Johnstone KA; Resnick JL; Holland AJ; Hagan JJ; Wilkinson LS; Isles AR. 2010. Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome. Eur J Neurosci 31(1):156-64. [PubMed: 20092561]  [MGI Ref ID J:158362]

de Los Santos T; Schweizer J; Rees CA; Francke U. 2000. Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from PWCR1, a novel imprinted gene in the prader-willi deletion region, which Is highly expressed in brain Am J Hum Genet 67(5):1067-82. [PubMed: 11007541]  [MGI Ref ID J:65556]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry

Paternal transmission of the PWS-ICdel mutation results in neonatal lethality between 1-7 days of age due to imprinting defects. For routine colony maintenance at The Jackson Laboratory Repository, heterozygous females are bred with wildtype males from the colony (or C57BL/6J inbred males); this results in offspring that are viable and fertile as adults. If researchers want to generate PWS-ICdel offspring with the neonatal lethality phenotype, wildtype females from the colony (or C57BL/6J inbred females) may be bred with heterozygous males; this results in paternal transmission of the PWS-ICdel mutation. Of note, removing all but one wildtype littermate improves mutant mouse survivability. In addition, mutant mouse viability may be greatly improved by outcrossing to FVB/NJ females.

Mating System

See Colony Maintenance under the Health & husbandry tab         (Female x Male)   26-OCT-11

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

 

This strain is currently Awaiting Transfer from the Donor.

View All Strains Awaiting Transfer from the Donor, In Progress and On Hold

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.

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