| |||||||||
Type Congenic; Mutant Strain; Targeted Mutation; Species laboratory 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.
| Allele | Control | |
|---|---|---|
| Cdkn1ctm1Sje | Wild-type from the colony | |
| Cdkn1ctm1Sje | 000664 C57BL/6J | |
| Considerations for Choosing Controls | ||
Congenic Nomenclature
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
| 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 Origin | 129S7/SvEvBrd-Hprt1 | ||
| ES Cell Line Name | AB2.1 | ||
| ES Cell Line Strain | 129S7/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 Protocols
Cdkn1ctm1Sje, SEP PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
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]
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]
Colony Maintenance
Breeding & Husbandry The 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
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| 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. | ||
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.
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form