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| Ndn-null mice harbor a maternally-inherited imprinted/silenced wildtype allele and a paternally-inherited Ndntm2Stw (ΔNdn-lacZ or Ndn-lacZ) knock-in allele that also abolishes endogenous Ndn (necdin) gene function. Ndn-null mice on this C57BL/6J genetic background recapitulate aspects of Prader-Willi syndrome; with defects in the forebrain and central/autonomic nervous system neurons that result in high levels of postnatal lethality from respiratory distress. | |||||||||||||||
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Description
Strain Information
Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x +/+ sibling (Female x Male) 20-FEB-10 Species laboratory mouse Generation N15+F1 (29-JUN-11)
Generation DefinitionsDonating Investigator Rachel Wevrick, University of Alberta Important Note
Maternal imprinting silences the Ndn gene.
For routine colony maintenance at The Jackson Laboratory Repository, heterozygous females are bred with wildtype males (or C57BL/6J inbred males); this results in offspring with no abnormal phenotype.
For researchers to obtain "Ndn-null" offspring (both maternal and paternal Ndn alleles are non-functional), wildtype females are bred with heterozygous males; this results in maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Ndn-lacZ (null) allele.Description
The mouse locus 7qB4/B5 (syntenic with the Prader-Willi region at chromosome position 15q11-q13 in humans) encompasses the cluster of paternally-expressed imprinted genes Magel2, Ndn, Mkrn3, and Peg12. As maternal imprinting silences the Ndn allele, only the paternally inherited Ndn allele is expressed. The Ndntm2Stw (ΔNdn-lacZ or Ndn-lacZ) knock-in allele abolishes endogenous gene function and expresses a β-galactosidase fusion protein. Under control of the upstream promoter/enhancer elements, lacZ expression is directed to the same tissues as the wildtype gene. For example, β-galactosidase expression during embryogenesis is highest in hypothalamus, but also detected in other central nervous system tissues (pons and medulla, spinal cord), peripheral nervous system (dorsal root ganglia), and some non-neuronal tissues (tongue, cartilage brown fat). Breeding heterozygous females with wildtype males (or C57BL/6J inbred males) results in offspring with no abnormal phenotype. To obtain "Ndn-null" offspring (both maternal and paternal Ndn alleles are non-functional), wildtype females are bred with heterozygous males; allowing maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Ndntm2Stw allele. Ndn-null mice on this C57BL/6J genetic background recapitulate aspects of Prader-Willi syndrome; with defects in the forebrain and central/autonomic nervous system neurons that result in high levels of postnatal lethality from respiratory distress.Development
A targeting vector was designed to fuse a β-galactosidase (lacZ) expression cassette (followed by a reverse-oriented loxP-flanked PGK-neo cassette) in-frame with the first 31 codons of the Ndn (necdin) locus, as well as delete the remaining Ndn open reading frame. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6 females to establish the Ndntm1Stw colony. To remove the floxed selection cassette, Ndntm1Stw mice were bred to MMTV-Cre mice (mixed 129Sv/FVB genetic background; see Stock No. 003553). The resulting Ndntm2Stw (ΔNdn-lacZ) mice were subsequently backcrossed to C57BL/6J for approximately 14 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
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).
Prader-Willi Syndrome; PWS
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Ndntm2Stw/Ndn+
involves: 129S1/Sv * C57BL/6J
- mortality/aging
- complete neonatal lethality
- mice inheriting the mutant allele paternally die a few hours after birth (MGI Ref ID J:82266)
- respiratory system phenotype
- abnormal respiration
- the respiratory motor discharge pattern produced by cervical ventral roots, hypoglossal roots, cranial motoneuron pools and within neurons located in the putative respiratory rhythm-generating center, the pre-Botzinger complex, is very irregular in mice inheriting the mutant allele from the father, with prominent bouts of depression of respiratory rhythmogenesis (MGI Ref ID J:82266)
- cellular phenotype
- maternal imprinting (MGI Ref ID J:82266)
- homeostasis/metabolism phenotype
- cyanosis
- in mutants with the paternally inherited allele (MGI Ref ID J:82266)
- hypoxia
- in mutants with the paternally inherited allele (MGI Ref ID J:82266)
- nervous system phenotype
- abnormal central pattern generator function
- pups with abnormal breathing fail to generate rhythmic motor bursts from cervical or hypoglossal nerve roots in vitro or generate a severely irregular rhythmic motor output (MGI Ref ID J:82266)
- abnormal pre-Botzinger complex physiology
- he respiratory motor discharge pattern produced by cervical ventral roots, hypoglossal roots, cranial motoneuron pools and within neurons located in the putative respiratory rhythm-generating center, the pre-Botzinger complex, is very irregular in mice inheriting the mutant allele from the father, with prominent bouts of depression of respiratory rhythmogenesis (MGI Ref ID J:82266)
Ndntm2Stw/Ndn+
involves: 129S1/Sv * C57BL/6
- mortality/aging
- postnatal lethality
- mice inheriting the paternal allele exhibit 98% lethality within 30 hours of birth (MGI Ref ID J:57890)
- respiratory system phenotype
- respiratory distress
- mutants inheriting the mutant allele paternally exhibit respiratory distress shortly after birth; dsypneic with contraction of accessory respiratory muscles and often die at the end of this phase (MGI Ref ID J:57890)
- a few minutes before death, the respiratory contraction frequency dropped from one gasp every 2 seconds to one every 10-15 seconds and hypotonia is observed (MGI Ref ID J:57890)
- cellular phenotype
- maternal imprinting
- mice inheriting the maternal allele are indistinguishable from wild-type, whereas those inheriting the paternal allele show 98% lethality within 30 hours of birth (MGI Ref ID J:57890)
- homeostasis/metabolism phenotype
- cyanosis
- observed in mice inheriting the mutant allele from the father (MGI Ref ID J:57890)
- muscle phenotype
- hypotonia
- hypotonia is observed a few minutes before death when the mutant allele is paternally inherited (MGI Ref ID J:57890)
This mouse can be used to support research in many areas including:
Developmental Biology Research
Imprinting
Internal/Organ Defects
lung
Perinatal Lethality
Homozygous
Internal/Organ Research
Lung Defects
Neurobiology Research
lacZ expression in neural tissue
Research Tools
lacZ Expression
Developmental Biology Research
transplantation marker for embryonic and adult tissue
Genetics Research
Tissue/Cell Markers
Tissue/Cell Markers: multiple
Tissue/Cell Markers: neurons
Neurobiology Research
cell marker
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Ndntm2Stw | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Colin L Stewart | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Ndn-null; | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| ES Cell Line Name | W9.5/W95 | ||
| ES Cell Line Strain | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Site of Expression | LacZ expression mimics that of the targeted wildtype gene. During embryogenesis is highest in hypothalamus, but also detected in other central nervous system tissues (pons and medulla, spinal cord), peripheral nervous system (dorsal root ganglia), and some non-neuronal tissues (tongue, cartilage brown fat). | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Molecular Note | The floxed neo cassette was excised from Ndntm1Stw via in vivo cre mediated recombination. Sequence encoding lacZ was left in place of protein coding sequence downstream of the endogenous codon 31. [MGI Ref ID J:57890] | ||
| Gene Symbol and Name | Ndn, necdin | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | AI528698; HsT16328; PWCR; Peg6; expressed sequence AI528698; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Ndn (tm2Stw/J) Sep PCR, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Burow K; Hedrick HJ; Rapp KG. 1977. Ak-1 Mouse News Lett 56:65. [MGI Ref ID J:13716]
Gerard M; Hernandez L; Wevrick R; Stewart CL. 1999. Disruption of the mouse necdin gene results in early post-natal lethality [see comments] Nat Genet 23(2):199-202. [PubMed: 10508517] [MGI Ref ID J:57890]
Additional References
Ndntm2Stw relatedAsai T; Liu Y; Di Giandomenico S; Bae N; Ndiaye-Lobry D; Deblasio A; Menendez S; Antipin Y; Reva B; Wevrick R; Nimer SD. 2012. Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells. Blood 120(8):1601-12. [PubMed: 22776820] [MGI Ref ID J:189173]
Bush JR; Wevrick R. 2010. Loss of Necdin impairs myosin activation and delays cell polarization. Genesis 48(9):540-53. [PubMed: 20665884] [MGI Ref ID J:164695]
Bush JR; Wevrick R. 2012. Loss of the Prader-Willi obesity syndrome protein necdin promotes adipogenesis. Gene 497(1):45-51. [PubMed: 22305984] [MGI Ref ID J:183684]
Bush JR; Wevrick R. 2008. The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation. Differentiation :. [PubMed: 18557765] [MGI Ref ID J:140436]
Lee S; Walker CL; Karten B; Kuny SL; Tennese AA; O'Neill MA; Wevrick R. 2005. Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 14(5):627-37. [PubMed: 15649943] [MGI Ref ID J:96395]
Pagliardini S; Ren J; Wevrick R; Greer JJ. 2005. Developmental abnormalities of neuronal structure and function in prenatal mice lacking the prader-willi syndrome gene necdin. Am J Pathol 167(1):175-91. [PubMed: 15972963] [MGI Ref ID J:99506]
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]
Ren J; Lee S; Pagliardini S; Gerard M; Stewart CL; Greer JJ; Wevrick R. 2003. Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice. J Neurosci 23(5):1569-73. [PubMed: 12629158] [MGI Ref ID J:82266]
Tennese AA; Gee CB; Wevrick R. 2008. Loss of the Prader-Willi syndrome protein necdin causes defective migration, axonal outgrowth, and survival of embryonic sympathetic neurons. Dev Dyn 237(7):1935-43. [PubMed: 18570257] [MGI Ref ID J:137167]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry Maternal imprinting silences the Ndn gene.
For routine colony maintenance at The Jackson Laboratory Repository, heterozygous females are bred with wildtype males (or C57BL/6J inbred males); this results in offspring with no abnormal phenotype.
For researchers to obtain "Ndn-null" offspring (both maternal and paternal Ndn alleles are non-functional), wildtype females are bred with heterozygous males; this results in maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Ndn-lacZ (null) allele.Mating System Heterozygote x +/+ sibling (Female x Male) 20-FEB-10 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Heterozygous for Ndntm2Stw
Price per Pair (US dollars $) Pair Genotype $296.00 Heterozygous for Ndntm2Stw x Wild-type for Ndntm2Stw $296.00 Wild-type for Ndntm2Stw x Heterozygous for Ndntm2Stw Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Heterozygous for Ndntm2Stw
Price per Pair (US dollars $) Pair Genotype $384.80 Heterozygous for Ndntm2Stw x Wild-type for Ndntm2Stw $384.80 Wild-type for Ndntm2Stw x Heterozygous for Ndntm2Stw Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
|
|
|
Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Important Note
Maternal imprinting silences the Ndn gene.For routine colony maintenance at The Jackson Laboratory Repository, heterozygous females are bred with wildtype males (or C57BL/6J inbred males); this results in offspring with no abnormal phenotype.
For researchers to obtain "Ndn-null" offspring (both maternal and paternal Ndn alleles are non-functional), wildtype females are bred with heterozygous males; this results in maternal transmission of the imprinted/silenced wildtype allele and paternal transmission of the Ndn-lacZ (null) allele.
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