Strain Name:

B6.129S7-Cdkn1ctm1Sje/J

Stock Number:

003336

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Purchasing Information

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129S7 via AB1 ES cell line (+Hprt-bm2)
 
Donating Investigator Stephen Elledge,   Baylor College of Medicine

Description
Mice lacking the Cdkn1c gene have altered cell proliferation and differentiation, leading to abdominal muscle defects; cleft palate; endochrondral bone ossification defects with incomplete differentiation of hypertrophic chondrocytes; renal medullary dysplasia; adrenal cortical hyperplasia and cytomegaly; lens cell hyperproliferation and apoptosis. The targeted gene is imprinted. The phenotype differs depending on whether the targeted allele is transmitted from the dam or the sire; maternal inheritance of the null allele is lethal. This is a model for the human Beckwith-Wiedemann syndrome.

Development
A targeting construct that removed exons 1 and 2 (87% of the p57KIP2 coding region) was introduced into AB2.1 embryonic stem cells. Homologous recombinant cells were injected into C57BL/6 blastocysts. Male chimeras were mated to C57BL/6 females. The disrupted allele is a null.

Control Information

  Allele   Control
 Cdkn1ctm1Sje  Wild-type from the colony
 Cdkn1ctm1Sje  000664 C57BL/6J
 
  Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

Related Disease (OMIM) Terms

Beckwith-Wiedemann Syndrome; BWS

Mammalian Phenotype Terms assigned by genotype

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

Cdkn1ctm1Sje/Cdkn1c+

        involves: 129S7/SvEvBrd * C57BL/6
  • lethality-prenatal/perinatal
  • lethality throughout fetal growth and development (MGI Ref ID J:104004)
    • present at expected numbers at E16.5
    • 30% die in utero before birth when Cdkn1ctm1Sje is maternally inherited
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:40203)
    • half expected numbers survive to 2 weeks of age
    • significant improvement in survival beyond day 1 of heterozygotes inheriting a maternal mutant when on an outbred CD1 backgound significant improvement in survival beyond day 1 of heterozygotes inheriting a maternal mutant when on an outbred CD1 backgound
  • endocrine/exocrine gland phenotype
  • enlarged adrenal glands (MGI Ref ID J:40203)
    • significantly enlarged and displaying cytomegaly
  • cellular phenotype
  • paternal imprinting (MGI Ref ID J:40203)
    • paternal allele is transcriptionally repressed
    • no abnormal phenotype in crosses between heterozygous males and wild-type females

Cdkn1ctm1Sje/Cdkn1c+

        involves: 129 * C57BL/6
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:108700)
    • mice that maternally inherit the mutant allele do not survive to adulthood

Cdkn1ctm1Sje/Cdkn1ctm1Sje

        involves: 129S7/SvEvBrd * C57BL/6
  • lethality-prenatal/perinatal
  • lethality throughout fetal growth and development (MGI Ref ID J:40203)
    • about 10% die between E13 and E16
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:40203)
    • no homozygotes survive to 2 weeks of age
  • growth/size phenotype
  • herniated abdominal wall (MGI Ref ID J:40203)
  • omphalocele (MGI Ref ID J:40203)
    • small intestine sometimes outside of the body wall
  • reduced fetal size (MGI Ref ID J:40203)
    • E18 mutants 10% shorter than control although skeletal length is normal
  • embryogenesis phenotype
  • omphalocele (MGI Ref ID J:40203)
    • small intestine sometimes outside of the body wall
  • digestive/alimentary phenotype
  • abnormal intestine morphology (MGI Ref ID J:40203)
    • air found in the stomach and intestines causing inflation
    • abnormal ileum morphology (MGI Ref ID J:40203)
      • found in front of the liver at E18.5
    • abnormal jejunum morphology (MGI Ref ID J:40203)
      • found in front of the liver at E18.5
  • cleft palate (MGI Ref ID J:40203)
    • failure of the palate to fuse is observed at E20
  • muscle phenotype
  • abnormal skeletal muscle morphology (MGI Ref ID J:40203)
    • abnormal musculature of the body wall, failing to approach the mid ventral line at the level of the umbilicus
  • respiratory system phenotype
  • respiratory distress (MGI Ref ID J:40203)
    • difficulty breathing in all neonates
    • milk found in the lungs
  • craniofacial phenotype
  • cleft palate (MGI Ref ID J:40203)
    • failure of the palate to fuse is observed at E20
  • renal/urinary system phenotype
  • *normal* renal/urinary system phenotype (MGI Ref ID J:104004)
    • glomeruli are normal at all stages of maturation
    • abnormal kidney medulla development (MGI Ref ID J:40203)
      • abnormal development at E16.5 and later
    • small inner medullary pyramid (MGI Ref ID J:40203)
      • fewer than normal renal tubules (loops of Henle and collecting ducts)
  • skeleton phenotype
  • abnormal long bone morphology (MGI Ref ID J:40203)
    • limb bones are shorter and thicker
    • abnormal long bone epiphysis morphology (MGI Ref ID J:40203)
      • columnar alignment of chondrocytes somewhat disorganized
      • thinner hypertrophic zone
      • higher rate of cell division in resting and proliferative chondrocytes at E15
    • decreased length of long bones (MGI Ref ID J:40203)
    • increased diameter of long bones (MGI Ref ID J:40203)
  • split sternum (MGI Ref ID J:40203)
    • delayed fusion and ossification
  • vision/eye phenotype
  • abnormal lens development (MGI Ref ID J:40203)
    • lens vacuolation by E15.5
  • increased lens epithelium apoptosis (MGI Ref ID J:40203)
    • 10 fold increase of apoptosis in the anterior epithelial compartment
  • limbs/digits/tail phenotype
  • abnormal long bone morphology (MGI Ref ID J:40203)
    • limb bones are shorter and thicker
    • abnormal long bone epiphysis morphology (MGI Ref ID J:40203)
      • columnar alignment of chondrocytes somewhat disorganized
      • thinner hypertrophic zone
      • higher rate of cell division in resting and proliferative chondrocytes at E15
    • decreased length of long bones (MGI Ref ID J:40203)
    • increased diameter of long bones (MGI Ref ID J:40203)
  • endocrine/exocrine gland phenotype
  • abnormal gland morphology (MGI Ref ID J:40203)

Cdkn1ctm1Sje/Cdkn1ctm1Sje

        either: (involves: 129S7/SvEvBrd * C57BL/6) or (involves: 129S7/SvEvBrd * ICR)
  • vision/eye phenotype
  • abnormal lens epithelium morphology (MGI Ref ID J:63217)
    • increased mitosis at E14.5 but not later or at E13.5
  • abnormal retina morphology (MGI Ref ID J:63217)
    • increased mitosis at E14.5 but not later or at E13.5
    • increased apoptosis as well

Research Applications

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

Cdkn1ctm1Sje related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Eye Defects
Growth Defects
Internal/Organ Defects (adrenal cortex)
Internal/Organ Defects (kidney)
Skeletal Defects

Internal/Organ Research
Adrenal Cortex Defects
Kidney Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol Cdkn1ctm1Sje
Allele Name targeted mutation 1, SJ Elledge
Common Name(s) p57+/-m; p57-; p57KIP2;
Mutation Made By Pumin Zhang,   Baylor College of Medicine
Strain of Origin129S7/SvEvBrd-Hprt1
ES Cell Line NameAB2.1
ES Cell Line Strain129S7/SvEvBrd-Hprt1
Gene Symbol and Name Cdkn1c, cyclin-dependent kinase inhibitor 1C (P57)
Chromosome 7
Gene Common Name(s) AL024410; BWCR; BWS; CDKI; KIP2; WBS; expressed sequence AL024410; p57; p57Kip2;
Molecular Note Replacement of exons 1 and 2 (87% of the Cdkn1c coding region) with a neomycin cassette. [MGI Ref ID J:40203]

Genotyping

Genotyping Information

Genotyping Protocols

Cdkn1ctm1Sje, SEP PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zhang P; Liegeois NJ; Wong C; Finegold M; Hou H; Thompson JC ; Silverman A ; Harper JW ; DePinho RA ; Elledge SJ. 1997. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature 387(6629):151-8. [PubMed: 9144284]  [MGI Ref ID J:40203]

Additional References

Cdkn1ctm1Sje related

Andrews SC; Wood MD; Tunster SJ; Barton SC; Surani MA; John RM. 2007. Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted domain on mouse distal chromosome 7. BMC Dev Biol 7:53. [PubMed: 17517131]  [MGI Ref ID J:126494]

Caspary T; Cleary MA; Perlman EJ; Zhang P; Elledge SJ; Tilghman SM. 1999. Oppositely imprinted genes p57(Kip2) and igf2 interact in a mouse model for Beckwith-Wiedemann syndrome. Genes Dev 13(23):3115-24. [PubMed: 10601037]  [MGI Ref ID J:58998]

Dyer MA; Cepko CL. 2000. p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development 127(16):3593-605. [PubMed: 10903183]  [MGI Ref ID J:63217]

Georgia S; Soliz R; Li M; Zhang P; Bhushan A. 2006. p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Dev Biol 298(1):22-31. [PubMed: 16899237]  [MGI Ref ID J:119274]

Gui H; Li S; Matise MP. 2007. A cell-autonomous requirement for Cip/Kip cyclin-kinase inhibitors in regulating neuronal cell cycle exit but not differentiation in the developing spinal cord. Dev Biol 301(1):14-26. [PubMed: 17123502]  [MGI Ref ID J:117093]

Hagan JP; Kozlov SV; Chiang Y; Sewell L; Stewart CL. 2004. Intraspecific mating with CzechII/Ei mice rescue lethality associated with loss of function mutations of the imprinted genes, Igf2r and Cdkn1c. Genomics 84(5):836-43. [PubMed: 15475262]  [MGI Ref ID J:118454]

Hiromura K; Haseley LA; Zhang P; Monkawa T; Durvasula R; Petermann AT; Alpers CE; Mundel P; Shankland SJ. 2001. Podocyte expression of the CDK-inhibitor p57 during development and disease. Kidney Int 60(6):2235-46. [PubMed: 11737597]  [MGI Ref ID J:104004]

Jin RJ; Lho Y; Wang Y; Ao M; Revelo MP; Hayward SW; Wills ML; Logan SK; Zhang P; Matusik RJ. 2008. Down-regulation of p57Kip2 induces prostate cancer in the mouse. Cancer Res 68(10):3601-8. [PubMed: 18483241]  [MGI Ref ID J:135026]

MacLean HE; Guo J; Knight MC; Zhang P; Cobrinik D; Kronenberg HM. 2004. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest 113(9):1334-43. [PubMed: 15124025]  [MGI Ref ID J:89721]

Mager J; Montgomery ND; de Villena FP; Magnuson T. 2003. Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet 33(4):502-7. [PubMed: 12627233]  [MGI Ref ID J:82790]

Mancini-Dinardo D; Steele SJ; Levorse JM; Ingram RS; Tilghman SM. 2006. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20(10):1268-82. [PubMed: 16702402]  [MGI Ref ID J:108700]

Vlachos P; Nyman U; Hajji N; Joseph B. 2007. The cell cycle inhibitor p57(Kip2) promotes cell death via the mitochondrial apoptotic pathway. Cell Death Differ 14(8):1497-507. [PubMed: 17464323]  [MGI Ref ID J:139269]

Zhang P; Wong C; DePinho RA; Harper JW; Elledge SJ. 1998. Cooperation between the Cdk inhibitors p27(KIP1) and p57(KIP2) in the control of tissue growth and development. Genes Dev 12(20):3162-7. [PubMed: 9784491]  [MGI Ref ID J:50769]

Zhang PM; Wong C; Liu D; Finegold M; Harper JW; Elledge SJ. 1999. p21(CIP1) and p57(KIP2) control muscle differentiation at the myogenin step. Genes Dev 13(2):213-224. [PubMed: 9925645]  [MGI Ref ID J:52552]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryThe strain originated on a 129/Sv background and is currently at N9 on a C57BL/6 background. The donating investigator maintains the strain by mating heterozygous males to C57BL/6 females. The protein Cdkn1c is encoded by a maternally expressed, imprinted gene in both mice and humans. Maternal inheritance of the null allele is lethal. Expected coat color from breeding:Black
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Allele   Control
 Cdkn1ctm1Sje  Wild-type from the colony
 Cdkn1ctm1Sje  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

View JAX® Mice & Services Conditions of Use.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.
Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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