Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F8+N1F9 N1p   Donating Investigator Matthew Fero,   Fred Hutchinson Cancer Research Center

Description
Mice deficient in p27^kip are viable, but are larger than normal littermates, with increased cellularity of all tissues. The thymus and spleen are particularly enlarged. Homozygous mutant, Cdkn1b-null adult mice have a shortened lifespan due to the growth of benign intermediate lobe pituitary tumors. Female mice are infertile, with a follicular phase ovulatory block. Large doses of exogenous gonadotropin induce ovulation, but both implantation and intrauterine embryonic development is impaired. The mice demonstrate haploid-insufficient susceptibility to the development of adenomas in the pituitary, intestine and lung following exposure to gamma irradiation or chemical carcinogens.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Cdkn1b^tm1Mlf allele

002781

B6.129S4-Cdkn1btm1Mlf/J

View Strains carrying   Cdkn1b^tm1Mlf     (1 strain)

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cdkn1b^tm1Mlf/Cdkn1b⁺

        involves: 129S4/SvJaeSor

• tumorigenesis
• increased incidence of chemically-induced tumors (MGI Ref ID J:103819)
  • similar increase in the incidence of urethane-induced lung tumors as homozygotes, with more large tumors than in wild-type
  • increased incidence of liver hemangiomas, uterine tumors, and ovarian granulose cell tumors after 20 weeks of urethane treatment, but less than in homozygotes
• homeostasis/metabolism phenotype
• increased incidence of chemically-induced tumors (MGI Ref ID J:103819)
  • similar increase in the incidence of urethane-induced lung tumors as homozygotes, with more large tumors than in wild-type
  • increased incidence of liver hemangiomas, uterine tumors, and ovarian granulose cell tumors after 20 weeks of urethane treatment, but less than in homozygotes

Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf

        involves: 129S4/SvJaeSor

• nervous system phenotype
• abnormal neurogenesis (MGI Ref ID J:109091)
  • cortex of mutant shows fewer neurons born on E14.5 that express differentiation markers at E17.5
  • reduction in differentiation is most prominent in VZ/SVZ
• abnormal neuronal migration (MGI Ref ID J:109091)
  • defect in cortical neuronal migration is observed at E17.5; fewer cells reach the cortical plate in mutants compared to wild-type
  • greater numbers of cells accumulates in the ventricular zone (VZ) and subventricular zone (SVZ) in mutants
  • radial migration is impaired in mutant cortices
• tumorigenesis
• increased incidence of chemically-induced tumors (MGI Ref ID J:103819)
  • increase in incidence of urethane-induced lung tumors compared to wild-type, with more large tumors than in heterozygotes
  • 100% penetrance of pituitary adenomas and harderian gland tumors after 20 weeks of urethane treatment, as well as increased incidence of liver hemangiomas, uterine tumors and ovarian granulose cell tumors
• immune system phenotype
• abnormal spleen cellularity (MGI Ref ID J:107588)
  • Cdkn1b-deficient mice show hypercellular spleens when receiving transplants of bone marrow from mutant or wild-type mice
• enlarged spleen (MGI Ref ID J:107588)
  • spleens are enlarged when recipients receive bone marrow cells from wild-type or mutant donors
• enlarged thymus (MGI Ref ID J:107588)
  • Cdkn1b-deficient mice develop hyperplastic thymuses when receiving bone marrow from wild-type or mutant donors
• hematopoietic system phenotype
• abnormal spleen cellularity (MGI Ref ID J:107588)
  • Cdkn1b-deficient mice show hypercellular spleens when receiving transplants of bone marrow from mutant or wild-type mice
• enlarged spleen (MGI Ref ID J:107588)
  • spleens are enlarged when recipients receive bone marrow cells from wild-type or mutant donors
• enlarged thymus (MGI Ref ID J:107588)
  • Cdkn1b-deficient mice develop hyperplastic thymuses when receiving bone marrow from wild-type or mutant donors
• homeostasis/metabolism phenotype
• increased incidence of chemically-induced tumors (MGI Ref ID J:103819)
  • increase in incidence of urethane-induced lung tumors compared to wild-type, with more large tumors than in heterozygotes
  • 100% penetrance of pituitary adenomas and harderian gland tumors after 20 weeks of urethane treatment, as well as increased incidence of liver hemangiomas, uterine tumors and ovarian granulose cell tumors

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

Cdkn1b^tm1Mlf/Cdkn1b⁺

        involves: 129S4/SvJaeSor * C57BL/6NHsd

• hearing/vestibular/ear phenotype
• increased cochlear inner hair cell number (MGI Ref ID J:53290)
  • at P6, heterozygotes display occasional supernumerary inner hair cells throughout the organ of Corti; never observed in wild-type mice
  • in contrast, the heterozygous outer hair cell population remains normal relative to wild-type mice
• nervous system phenotype
• increased cochlear inner hair cell number (MGI Ref ID J:53290)
  • at P6, heterozygotes display occasional supernumerary inner hair cells throughout the organ of Corti; never observed in wild-type mice
  • in contrast, the heterozygous outer hair cell population remains normal relative to wild-type mice

Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf

        involves: 129S4/SvJaeSor * C57BL/6J

• growth/size phenotype
• increased body weight (MGI Ref ID J:33400)
  • body weight increase becomes evident between 2-3 weeks of age, is maximal by 10 weeks of age, and is maintained throughout adulthood and is partly attributable to enlargement of all internal organs, however do not have an increase in body fat amount
• tumorigenesis
• pituitary adenoma (MGI Ref ID J:33400)
  • adenomatous, neoplastic transformation of the pars intermedia
• life span-post-weaning/aging
• premature death (MGI Ref ID J:33400)
  • no indication of early mortality at 9 months of age on the mixed 129/Sv and C57BL/6J background, however on a 129/Sv background, majority die with massively enlarged pituitary tumors
• endocrine/exocrine gland phenotype
• absent corpus luteum (MGI Ref ID J:33400)
  • secondary ovarian follicles develop but do not progress to form corpora lutea
• enlarged pituitary gland (MGI Ref ID J:33400)
  • disproportionately enlarged
• pituitary gland hyperplasia (MGI Ref ID J:33400)
  • gross hyperplasia becomes evident at 8-10 weeks of age
• immune system phenotype
• abnormal spleen morphology (MGI Ref ID J:33400)
• enlarged spleen (MGI Ref ID J:33400)
  • disproportionately enlarged
• spleen hyperplasia (MGI Ref ID J:33400)
  • becomes evident by 4 weeks of age
• abnormal thymus morphology (MGI Ref ID J:33400)
• enlarged thymus (MGI Ref ID J:33400)
  • disproportionately enlarged
• thymus hyperplasia (MGI Ref ID J:33400)
  • becomes evident by 4 weeks of age
  • 3-fold increase in the number of thymocytes, however development of thymocytes is normal
• increased T cell proliferation (MGI Ref ID J:33400)
  • thymoblasts and splenic T cells have an increase in percentage of S phase cells and a 3-4-fold increase in cyclin E-associated kinase activity, indicating increased cell proliferation
• hematopoietic system phenotype
• abnormal hematopoiesis (MGI Ref ID J:33400)
  • increase in the number of granulocyte-macrophage, early and late erythroid progenitors, and megakaryotic progenitors in both the marrow and spleen
• increased T cell proliferation (MGI Ref ID J:33400)
  • thymoblasts and splenic T cells have an increase in percentage of S phase cells and a 3-4-fold increase in cyclin E-associated kinase activity, indicating increased cell proliferation
• abnormal spleen morphology (MGI Ref ID J:33400)
• enlarged spleen (MGI Ref ID J:33400)
  • disproportionately enlarged
• spleen hyperplasia (MGI Ref ID J:33400)
  • becomes evident by 4 weeks of age
• abnormal thymus morphology (MGI Ref ID J:33400)
• enlarged thymus (MGI Ref ID J:33400)
  • disproportionately enlarged
• thymus hyperplasia (MGI Ref ID J:33400)
  • becomes evident by 4 weeks of age
  • 3-fold increase in the number of thymocytes, however development of thymocytes is normal
• liver/biliary system phenotype
• abnormal hepatocyte morphology (MGI Ref ID J:33400)
  • average of 23% increase in hepatocyte cell density
• reproductive system phenotype
• absent corpus luteum (MGI Ref ID J:33400)
  • secondary ovarian follicles develop but do not progress to form corpora lutea
• female infertility (MGI Ref ID J:33400)
  • females do not become pregnant, however, exogenous administration of gonadotropins induced ovulation, differentiation of the corpora lutea, and early development of viable embryos, with embryos implanting but not developing to term
• vision/eye phenotype
• abnormal retinal neuronal layer morphology (MGI Ref ID J:33400)
  • loss of the normally sharp boundary between the inner and outer nuclear layer
• disorganized retinal layers (MGI Ref ID J:33400)
  • subtle disorganization of the retina
• nervous system phenotype
• abnormal cerebral cortex morphology (MGI Ref ID J:33400)
  • about 30% increase in neuronal cell density in the cerebral cortex
• abnormal epithalamus morphology (MGI Ref ID J:33400)
  • about 30% increase in neuronal cell density in the habenular nucleus
• abnormal hippocampus morphology (MGI Ref ID J:33400)
  • about 30% increase in neuronal cell density in the hippocampus
• enlarged pituitary gland (MGI Ref ID J:33400)
  • disproportionately enlarged
• pituitary gland hyperplasia (MGI Ref ID J:33400)
  • gross hyperplasia becomes evident at 8-10 weeks of age

Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf

        involves: 129S4/SvJaeSor * C57BL/6NHsd

• growth/size phenotype
• increased body size (MGI Ref ID J:53290)
  • homozygotes are larger than wild-type littermates as a result of multiorgan hyperplasia
• hearing/vestibular/ear phenotype
• abnormal organ of Corti (MGI Ref ID J:53290)
  • at P6, homozygotes exhibit hyperplasia of the organ of Corti
  • continued presence of proliferating cells in the postnatal organ of Corti, as well as abnormal persistence of Cdkn1b expression in mature supporting cells indicate a role for Cdkn1b in maintaining these cells in a quiescent state
• abnormal pillar cell morphology (MGI Ref ID J:53290)
  • at P6, homozygotes display supernumerary cells in the pillar cell region of the organ of Corti, where normally one inner pillar and one outer pillar cells are present in wild-type mice
• increased cochlear hair cell number (MGI Ref ID J:53290)
  • homozygotes develop supernumerary hair cells in both the inner and outer rows of hair cells
• increased cochlear inner hair cell number (MGI Ref ID J:53290)
  • at P6, the mutant inner row contains a partly disorganized line of at most two hair cells, whereas wild-type mice normally contain a single row of inner hair cells
  • in homozygotes, IHC numbers are increased by a mean of 23% relative to wild-type mice
• increased cochlear outer hair cell number (MGI Ref ID J:53290)
  • at P6, homozygotes contain four, partly disorganized, rows of cochlear outer hair cells (OHCs) instead of the expected three rows of OHCs seen in wild-type mice
  • in homozygotes, OHC numbers are increased by a mean of 36% relative to wild-type mice
• increased supporting cell number (MGI Ref ID J:53290)
  • homozygotes develop an excess number of supporting cells, including pillar cells, separating IHCs from OHCs and occupying the area of the tunnel of Corti
• decreased brainstem auditory evoked potential (MGI Ref ID J:53290)
  • at 10 weeks of age, homozygotes display a significantly elevated mean, click-evoked, ABR threshold (77 db SPL) relative to age-matched wild-type mice (20 db SPL)
• impaired hearing (MGI Ref ID J:53290)
  • at 10 weeks of age, homozygotes are severely hearing-impaired
• nervous system phenotype
• increased cochlear hair cell number (MGI Ref ID J:53290)
  • homozygotes develop supernumerary hair cells in both the inner and outer rows of hair cells
• increased cochlear inner hair cell number (MGI Ref ID J:53290)
  • at P6, the mutant inner row contains a partly disorganized line of at most two hair cells, whereas wild-type mice normally contain a single row of inner hair cells
  • in homozygotes, IHC numbers are increased by a mean of 23% relative to wild-type mice
• increased cochlear outer hair cell number (MGI Ref ID J:53290)
  • at P6, homozygotes contain four, partly disorganized, rows of cochlear outer hair cells (OHCs) instead of the expected three rows of OHCs seen in wild-type mice
  • in homozygotes, OHC numbers are increased by a mean of 36% relative to wild-type mice
• cellular phenotype
• abnormal cell proliferation (MGI Ref ID J:53290)
  • at E16, anti-PCNA staining of the organ of Corti indicates that proliferation of sensory cell progenitors abnormally continues after E14 (i.e. past the normal time of cell cycle withdrawal), leading to the appearance of supernumerary hair cells and supporting cells in mutant mice
  • at E16, PCNA-positive cells are observed in the Deiters' cell region beneath the newly differentiated hair cells stained with anti-myosin VIIa
  • at P6, PCNA-positive cells are no longer seen in Deiters' cell region as they are at E16, but appear in clusters in the region of Hensen's cells, lateral to the outermost row of OHCs, as well as in the pillar cell regions separating IHCs and OHCs
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:53290)
  • no obvious behavioral defects related to vestibular function, such as circling or balance deficits, are observed

View Research Applications

Research Applications

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

Cdkn1b^tm1Mlf related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Reproductive Biology Research
Fertility Defects (females only)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cdkn1btm1Mlf
Allele Name		targeted mutation 1, Matthew Fero
Allele Type		Targeted (knock-out)
Common Name(s)		Cdkln1btm1Mlf; p27-; p27Kip1-; p27Kip1; p27kip1-null;
Mutation Made By		Matthew Fero,   Fred Hutchinson Cancer Research Center
Strain of Origin		129S4/SvJaeSor
ES Cell Line Name		AK7
ES Cell Line Strain		129S4/SvJaeSor
Gene Symbol and Name		Cdkn1b, cyclin-dependent kinase inhibitor 1B
Chromosome		6
Gene Common Name(s)		AA408329; AI843786; CDKN4; Cdki1b; KIP1; MEN1B; MEN4; P27KIP1; expressed sequence AA408329; expressed sequence AI843786; p27;
Molecular Note		Replacement of the entire coding region of the Cdkn1b gene with a neomycin cassette. [MGI Ref ID J:33400]

Genotyping

Genotyping Information

Genotyping Protocols

Cdkn1b^tm1Mlf, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Fero ML; Rivkin M; Tasch M; Porter P; Carow CE; Firpo E; Polyak K; Tsai LH; Broudy V; Perlmutter RM; Kaushansky K; Roberts JM. 1996. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 85(5):733-44. [PubMed: 8646781]  [MGI Ref ID J:33400]

Additional References

Lowenheim H; Furness DN; Kil J; Zinn C; Gultig K; Fero ML; Frost D; Gummer AW; Roberts JM; Rubel EW; Hackney CM; Zenner HP. 1999. Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti. Proc Natl Acad Sci U S A 96(7):4084-8. [PubMed: 10097167]  [MGI Ref ID J:54085]

McArthur GA; Foley KP; Fero ML; Walkley CR; Deans AJ; Roberts JM; Eisenman RN. 2002. MAD1 and p27(KIP1) cooperate to promote terminal differentiation of granulocytes and to inhibit Myc expression and cyclin E-CDK2 activity. Mol Cell Biol 22(9):3014-23. [PubMed: 11940659]  [MGI Ref ID J:78929]

Cdkn1b^tm1Mlf related

Besson A; Gurian-West M; Chen X; Kelly-Spratt KS; Kemp CJ; Roberts JM. 2006. A pathway in quiescent cells that controls p27Kip1 stability, subcellular localization, and tumor suppression. Genes Dev 20(1):47-64. [PubMed: 16391232]  [MGI Ref ID J:103819]

Besson A; Hwang HC; Cicero S; Donovan SL; Gurian-West M; Johnson D; Clurman BE; Dyer MA; Roberts JM. 2007. Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype. Genes Dev 21(14):1731-46. [PubMed: 17626791]  [MGI Ref ID J:123168]

Bryja V; Pachernik J; Faldikova L; Krejci P; Pogue R; Nevriva I; Dvorak P; Hampl A. 2004. The role of p27(Kip1) in maintaining the levels of D-type cyclins in vivo. Biochim Biophys Acta 1691(2-3):105-16. [PubMed: 15110991]  [MGI Ref ID J:89375]

Casanovas O; Hager JH; Chun MG; Hanahan D. 2005. Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis. Oncogene 24(44):6597-604. [PubMed: 16007165]  [MGI Ref ID J:101759]

Chen P; Segil N. 1999. p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti. Development 126(8):1581-90. [PubMed: 10079221]  [MGI Ref ID J:53290]

Chen P; Zindy F; Abdala C; Liu F; Li X; Roussel MF; Segil N. 2003. Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d. Nat Cell Biol 5(5):422-6. [PubMed: 12717441]  [MGI Ref ID J:83482]

Cheng N; van de Wetering CI; Knudson CM. 2008. p27 deficiency cooperates with Bcl-2 but not Bax to promote T-cell lymphoma. PLoS ONE 3(4):e1911. [PubMed: 18382684]  [MGI Ref ID J:134259]

Chien WM; Garrison K; Caufield E; Orthel J; Dill J; Fero ML. 2007. Differential gene expression of p27Kip1 and Rb knockout pituitary tumors associated with altered growth and angiogenesis. Cell Cycle 6(6):750-7. [PubMed: 17361101]  [MGI Ref ID J:133446]

Chien WM; Rabin S; Macias E; Miliani de Marval PL; Garrison K; Orthel J; Rodriguez-Puebla M; Fero ML. 2006. Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1. Proc Natl Acad Sci U S A 103(11):4122-7. [PubMed: 16537495]  [MGI Ref ID J:107588]

Cunningham JJ; Levine EM; Zindy F; Goloubeva O; Roussel MF; Smeyne RJ. 2002. The Cyclin-Dependent Kinase Inhibitors p19(Ink4d) and p27(Kip1) Are Coexpressed in Select Retinal Cells and Act Cooperatively to Control Cell Cycle Exit. Mol Cell Neurosci 19(3):359-74. [PubMed: 11906209]  [MGI Ref ID J:75882]

Davison EA; Lee CS; Naylor MJ; Oakes SR; Sutherland RL; Hennighausen L; Ormandy CJ; Musgrove EA. 2003. The cyclin-dependent kinase inhibitor p27 (Kip1) regulates both DNA synthesis and apoptosis in mammary epithelium but is not required for its functional development during pregnancy. Mol Endocrinol 17(12):2436-47. [PubMed: 12933906]  [MGI Ref ID J:125429]

Deans AJ; Simpson KJ; Trivett MK; Brown MA; McArthur GA. 2004. Brca1 inactivation induces p27(Kip1)-dependent cell cycle arrest and delayed development in the mouse mammary gland. Oncogene 23(36):6136-45. [PubMed: 15208652]  [MGI Ref ID J:91869]

Defoe DM; Adams LB; Sun J; Wisecarver SN; Levine EM. 2007. Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation. Mol Vis 13:273-86. [PubMed: 17356514]  [MGI Ref ID J:121480]

Diez-Juan A; Andres V. 2001. The growth suppressor p27(Kip1) protects against diet-induced atherosclerosis. FASEB J 15(11):1989-95. [PubMed: 11532979]  [MGI Ref ID J:120150]

Dyer MA; Cepko CL. 2000. Control of Muller glial cell proliferation and activation following retinal injury. Nat Neurosci 3(9):873-80. [PubMed: 10966617]  [MGI Ref ID J:109384]

Dyer MA; Cepko CL. 2001. p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci 21(12):4259-71. [PubMed: 11404411]  [MGI Ref ID J:124435]

Ellis FH Jr; Xu X; Kulke MH; Locicero J 3rd; Loda M. 2001. Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice. J Thorac Cardiovasc Surg 122(4):809-14. [PubMed: 11581618]  [MGI Ref ID J:71702]

Fero ML; Randel E; Gurley KE; Roberts JM; Kemp CJ. 1998. The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 396(6707):177-80. [PubMed: 9823898]  [MGI Ref ID J:50966]

Garrett-Engele CM; Tasch MA; Hwang HC; Fero ML; Perlmutter RM; Clurman BE; Roberts JM. 2007. A mechanism misregulating p27 in tumors discovered in a functional genomic screen. PLoS Genet 3(12):e219. [PubMed: 18069898]  [MGI Ref ID J:133427]

Gary B; Azuero R; Mohanty GS; Bell WC; Eltoum IE; Abdulkadir SA. 2004. Interaction of Nkx3.1 and p27kip1 in prostate tumor initiation. Am J Pathol 164(5):1607-14. [PubMed: 15111307]  [MGI Ref ID J:89571]

Geng Y; Yu Q; Sicinska E; Das M; Bronson RT; Sicinski P. 2001. Deletion of the p27Kip1 gene restores normal development in cyclin D1-deficient mice. Proc Natl Acad Sci U S A 98(1):194-9. [PubMed: 11134518]  [MGI Ref ID J:66707]

Georgia S; Bhushan A. 2006. p27 Regulates the transition of beta-cells from quiescence to proliferation. Diabetes 55(11):2950-6. [PubMed: 17065330]  [MGI Ref ID J:116542]

Green ES; Stubbs JL; Levine EM. 2003. Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators. Development 130(3):539-52. [PubMed: 12490560]  [MGI Ref ID J:84911]

Hauck L; Harms C; Rohne J; Gertz K; Dietz R; Endres M; von Harsdorf R. 2008. Protein kinase CK2 links extracellular growth factor signaling with the control of p27(Kip1) stability in the heart. Nat Med 14(3):315-24. [PubMed: 18311148]  [MGI Ref ID J:133681]

Hwang HC; Martins CP; Bronkhorst Y; Randel E; Berns A; Fero M; Clurman BE. 2002. Identification of oncogenes collaborating with p27Kip1 loss by insertional mutagenesis and high-throughput insertion site analysis. Proc Natl Acad Sci U S A 99(17):11293-8. [PubMed: 12151601]  [MGI Ref ID J:78518]

Jackson RJ; Adnane J; Coppola D; Cantor A; Sebti SM; Pledger WJ. 2002. Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models. Oncogene 21(55):8486-97. [PubMed: 12466968]  [MGI Ref ID J:80271]

Jones BW; Watt CB; Frederick JM; Baehr W; Chen CK; Levine EM; Milam AH; Lavail MM; Marc RE. 2003. Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol 464(1):1-16. [PubMed: 12866125]  [MGI Ref ID J:84675]

Kang-Decker N; Tong C; Boussouar F; Baker DJ; Xu W; Leontovich AA; Taylor WR; Brindle PK; van Deursen JM. 2004. Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer Cell 5(2):177-89. [PubMed: 14998493]  [MGI Ref ID J:88323]

King TJ; Gurley KE; Prunty J; Shin JL; Kemp CJ; Lampe PD. 2005. Deficiency in the gap junction protein connexin32 alters p27Kip1 tumor suppression and MAPK activation in a tissue-specific manner. Oncogene 24(10):1718-26. [PubMed: 15608667]  [MGI Ref ID J:97211]

King TJ; Lampe PD. 2005. Altered tumor biology and tumorigenesis in irradiated and chemical carcinogen-treated single and combined connexin32/p27Kip1-deficient mice. Cell Commun Adhes 12(5-6):293-305. [PubMed: 16531324]  [MGI Ref ID J:110392]

Kossatz U; Dietrich N; Zender L; Buer J; Manns MP; Malek NP. 2004. Skp2-dependent degradation of p27kip1 is essential for cell cycle progression. Genes Dev 18(21):2602-7. [PubMed: 15520280]  [MGI Ref ID J:93442]

Lee Y; Miller HL; Jensen P; Hernan R; Connelly M; Wetmore C; Zindy F; Roussel MF; Curran T; Gilbertson RJ; McKinnon PJ. 2003. A molecular fingerprint for medulloblastoma. Cancer Res 63(17):5428-37. [PubMed: 14500378]  [MGI Ref ID J:86085]

Lin J; Della-Fera MA; Li C; Page K; Choi YH; Hartzell DL; Baile CA. 2003. P27 knockout mice: reduced myostatin in muscle and altered adipogenesis. Biochem Biophys Res Commun 300(4):938-42. [PubMed: 12559964]  [MGI Ref ID J:113633]

Livne-Bar I; Pacal M; Cheung MC; Hankin M; Trogadis J; Chen D; Dorval KM; Bremner R. 2006. Chx10 is required to block photoreceptor differentiation but is dispensable for progenitor proliferation in the postnatal retina. Proc Natl Acad Sci U S A 103(13):4988-93. [PubMed: 16547132]  [MGI Ref ID J:107659]

Lowenheim H; Furness DN; Kil J; Zinn C; Gultig K; Fero ML; Frost D; Gummer AW; Roberts JM; Rubel EW; Hackney CM; Zenner HP. 1999. Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti. Proc Natl Acad Sci U S A 96(7):4084-8. [PubMed: 10097167]  [MGI Ref ID J:54085]

Macias E; de Marval PL; Senderowicz A; Cullen J; Rodriguez-Puebla ML. 2008. Expression of CDK4 or CDK2 in mouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis. Cancer Res 68(1):162-71. [PubMed: 18172308]  [MGI Ref ID J:131035]

Majumder PK; Grisanzio C; O'Connell F; Barry M; Brito JM; Xu Q; Guney I; Berger R; Herman P; Bikoff R; Fedele G; Baek WK; Wang S; Ellwood-Yen K; Wu H; Sawyers CL; Signoretti S; Hahn WC; Loda M; Sellers WR. 2008. A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression. Cancer Cell 14(2):146-55. [PubMed: 18691549]  [MGI Ref ID J:139572]

Malaterre J; Carpinelli M; Ernst M; Alexander W; Cooke M; Sutton S; Dworkin S; Heath JK; Frampton J; McArthur G; Clevers H; Hilton D; Mantamadiotis T; Ramsay RG. 2007. c-Myb is required for progenitor cell homeostasis in colonic crypts. Proc Natl Acad Sci U S A 104(10):3829-34. [PubMed: 17360438]  [MGI Ref ID J:120056]

Martin-Caballero J; Flores JM; Garcia-Palencia P; Collado M; Serrano M. 2004. Different cooperating effect of p21 or p27 deficiency in combination with INK4a/ARF deletion in mice. Oncogene 23(50):8231-7. [PubMed: 15378017]  [MGI Ref ID J:93856]

Martins RA; Zindy F; Donovan S; Zhang J; Pounds S; Wey A; Knoepfler PS; Eisenman RN; Roussel MF; Dyer MA. 2008. N-myc coordinates retinal growth with eye size during mouse development. Genes Dev 22(2):179-93. [PubMed: 18198336]  [MGI Ref ID J:131387]

McArthur GA; Foley KP; Fero ML; Walkley CR; Deans AJ; Roberts JM; Eisenman RN. 2002. MAD1 and p27(KIP1) cooperate to promote terminal differentiation of granulocytes and to inhibit Myc expression and cyclin E-CDK2 activity. Mol Cell Biol 22(9):3014-23. [PubMed: 11940659]  [MGI Ref ID J:78929]

Muzumdar MD; Luo L; Zong H. 2007. Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM). Proc Natl Acad Sci U S A 104(11):4495-500. [PubMed: 17360552]  [MGI Ref ID J:120052]

Nguyen L; Besson A; Heng JI; Schuurmans C; Teboul L; Parras C; Philpott A; Roberts JM; Guillemot F. 2006. p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev 20(11):1511-24. [PubMed: 16705040]  [MGI Ref ID J:109091]

Ophascharoensuk V; Fero ML; Hughes J; Roberts JM; Shankland SJ. 1998. The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury. Nat Med 4(5):575-80. [PubMed: 9585231]  [MGI Ref ID J:47416]

Payne SR; Zhang S; Tsuchiya K; Moser R; Gurley KE; Longton G; deBoer J; Kemp CJ. 2008. p27kip1 deficiency impairs G2/M arrest in response to DNA damage, leading to an increase in genetic instability. Mol Cell Biol 28(1):258-68. [PubMed: 17954563]  [MGI Ref ID J:128928]

Philipp J; Vo K; Gurley KE; Seidel K; Kemp CJ. 1999. Tumor suppression by p27Kip1 and p21Cip1 during chemically induced skin carcinogenesis. Oncogene 18(33):4689-98. [PubMed: 10467416]  [MGI Ref ID J:57034]

Philipp-Staheli J; Kim KH; Liggitt D; Gurley KE; Longton G; Kemp CJ. 2004. Distinct roles for p53, p27Kip1, and p21Cip1 during tumor development. Oncogene 23(4):905-13. [PubMed: 14647411]  [MGI Ref ID J:87536]

Philipp-Staheli J; Kim KH; Payne SR; Gurley KE; Liggitt D; Longton G; Kemp CJ. 2002. Pathway-specific tumor suppression. Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice. Cancer Cell 1(4):355-68. [PubMed: 12086850]  [MGI Ref ID J:77135]

Powell JD; Bruniquel D; Schwartz RH. 2001. TCR engagement in the absence of cell cycle progression leads to T cell anergy independent of p27(Kip1). Eur J Immunol 31(12):3737-46. [PubMed: 11745394]  [MGI Ref ID J:115423]

Rajareddy S; Reddy P; Du C; Liu L; Jagarlamudi K; Tang W; Shen Y; Berthet C; Peng SL; Kaldis P; Liu K. 2007. p27kip1 (Cyclin-Dependent Kinase Inhibitor 1B) Controls Ovarian Development by Suppressing Follicle Endowment and Activation and Promoting Follicle Atresia in Mice. Mol Endocrinol 21(9):2189-202. [PubMed: 17565040]  [MGI Ref ID J:124128]

Rowell EA; Walsh MC; Wells AD. 2005. Opposing roles for the cyclin-dependent kinase inhibitor p27kip1 in the control of CD4+ T cell proliferation and effector function. J Immunol 174(6):3359-68. [PubMed: 15749868]  [MGI Ref ID J:97698]

Rowell EA; Wang L; Hancock WW; Wells AD. 2006. The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation tolerance induced by costimulatory blockade. J Immunol 177(8):5169-76. [PubMed: 17015702]  [MGI Ref ID J:139450]

Scatizzi JC; Hutcheson J; Bickel E; Woods JM; Klosowska K; Moore TL; Haines GK rd; Perlman H. 2006. p21Cip1 is required for the development of monocytes and their response to serum transfer-induced arthritis. Am J Pathol 168(5):1531-41. [PubMed: 16651620]  [MGI Ref ID J:108569]

Sharov AA; Sharova TY; Mardaryev AN; di Vignano AT; Atoyan R; Weiner L; Yang S; Brissette JL; Dotto GP; Botchkarev VA. 2006. Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes. Proc Natl Acad Sci U S A 103(48):18166-71. [PubMed: 17114283]  [MGI Ref ID J:117080]

Short JD; Houston KD; Dere R; Cai SL; Kim J; Johnson CL; Broaddus RR; Shen J; Miyamoto S; Tamanoi F; Kwiatkowski D; Mills GB; Walker CL. 2008. AMP-activated protein kinase signaling results in cytoplasmic sequestration of p27. Cancer Res 68(16):6496-506. [PubMed: 18701472]  [MGI Ref ID J:139145]

Soeiro I; Mohamedali A; Romanska HM; Lea NC; Child ES; Glassford J; Orr SJ; Roberts C; Naresh KN; Lalani el-N; Mann DJ; Watson RJ; Thomas NS; Lam EW. 2006. p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo. Mol Cell Biol 26(16):6170-84. [PubMed: 16880527]  [MGI Ref ID J:111578]

Stehr W; Bernal NP; Erwin CR; Bernabe KQ; Guo J; Warner BW. 2006. Roles for p21waf1/cip1 and p27kip1 during the adaptation response to massive intestinal resection. Am J Physiol Gastrointest Liver Physiol 290(5):G933-41. [PubMed: 16322092]  [MGI Ref ID J:111081]

Sun D; Ren H; Oertel M; Sellers RS; Zhu L. 2007. Loss of p27Kip1 enhances tumor progression in chronic hepatocyte injury-induced liver tumorigenesis with widely ranging effects on Cdk2 or Cdc2 activation. Carcinogenesis 28(9):1859-66. [PubMed: 17434927]  [MGI Ref ID J:125423]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Trumpp A; Refaeli Y; Oskarsson T; Gasser S; Murphy M; Martin GR; Bishop JM. 2001. c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414(6865):768-73. [PubMed: 11742404]  [MGI Ref ID J:73369]

Verdoodt B; Blazek T; Rauch P; Schuler G; Steinkasserer A; Lutz MB; Funk JO. 2003. The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy. Eur J Immunol 33(11):3154-63. [PubMed: 14579284]  [MGI Ref ID J:86442]

Wolf G; Schanze A; Stahl RA; Shankland SJ; Amann K. 2005. p27(Kip1) Knockout mice are protected from diabetic nephropathy: evidence for p27(Kip1) haplotype insufficiency. Kidney Int 68(4):1583-9. [PubMed: 16164635]  [MGI Ref ID J:114430]

Zhang S; Lawless VA; Kaplan MH. 2000. Cytokine-stimulated T lymphocyte proliferation is regulated by p27Kip1. J Immunol 165(11):6270-7. [PubMed: 11086062]  [MGI Ref ID J:112128]

Zindy F; Cunningham JJ; Sherr CJ; Jogal S; Smeyne RJ; Roussel MF. 1999. Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases. Proc Natl Acad Sci U S A 96(23):13462-7. [PubMed: 10557343]  [MGI Ref ID J:58522]

Zindy F; Knoepfler PS; Xie S; Sherr CJ; Eisenman RN; Roussel MF. 2006. N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci U S A 103(31):11579-83. [PubMed: 16864777]  [MGI Ref ID J:111800]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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

	Control
	Wild-type from the colony
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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Ordering and Purchasing Information

      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

Terms of Use

Terms of Use

General Terms and Conditions

OncoMouse^® requires a license from DuPont, see Licenses for Strains with OncoMouse^® Technology.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.