STOCK Cdk4tm2.1Bbd/Cnbc

Status

Available to order

EMMA IDEM:08029
International strain nameSTOCK Cdk4tm2.1Bbd/Cnbc
Alternative nameCdk4 Cdk4 KO
Strain typeTargeted Mutant Strains : Knock-out
Allele/Transgene symbolCdk4tm2.1Bbd
Gene/Transgene symbolCdk4

Information from provider

ProviderMariano Barbacid
Provider affiliationMolecular Oncology, Centro Nacional de Investigaciones Oncologicas
Genetic informationAn frt site was inserted 230 bp upstream of exon 2 and a PGK-hygromycin cassette flanked by frt sites was inserted 115 bp downstream of exon 4. The PGK-hygromycin cassette and exons 2-4 of Cdk4 were excised by Flp-mediated recombination. This is the resulting knock-out mouse line, after frt-mediated exon excision.
Phenotypic informationHomozygous:
Flp-mediated excision of exons 2-4 creates a null allele for Cdk4. Homozygous mice for the null allele have smaller size, noticeable at birth and progressively more noticeable with age. Mice develop diabetes after 2 months of age due to a drastic reduction in pancreatic beta cell numbers and islet size. Complete infertility in females and partial infertility in males is also observed. Reduction in pituitary gland size and pituitary-hormones production.

Heterozygous:
Heterozygous mice are viable
Breeding historyChimeras were crossed with CD1 females for germ line transmission analysis. Heterozygous animals for the three-frt sites allele were crossed with transgenic CAG-Flp mice to excise the frt-PGKneo-frt cassette and exons 2-4 of Cdk4. Line was maintained by inter-crossing heterozygous animals for the Cdk4 null allele. Genetic background involves 129S1/Sv, 129X1/SvJ, CD1 and C57BL/6J.
References
  • Mice thrive without Cdk4 and Cdk2.;Barrière Cédric, Santamaría David, Cerqueira Antonio, Galán Javier, Martín Alberto, Ortega Sagrario, Malumbres Marcos, Dubus Pierre, Barbacid Mariano, ;2007;Molecular oncology;1;72-83; 19383288
  • A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.;Puyol Marta, Martín Alberto, Dubus Pierre, Mulero Francisca, Pizcueta Pilar, Khan Gulfaraz, Guerra Carmen, Santamaría David, Barbacid Mariano, ;2010;Cancer cell;18;63-73; 20609353
Homozygous fertileno
Homozygous viableyes
Homozygous matings requiredno
Immunocompromisedno

Information from EMMA

Archiving centreCNB-CSIC, Centro Nacional de Biotecnologia, Madrid, Spain
Animals used for archivingheterozygous C57BL/6J

Disease and phenotype information

IMPC phenotypes (gene matching)
  • hypoplasia / IMPC
  • abnormal embryo size / IMPC
  • preweaning lethality, incomplete penetrance / IMPC
  • developmental dysplasia / IMPC
  • decreased body length / IMPC
  • edema / IMPC
  • female infertility / IMPC
  • microphthalmia / IMPC
  • male infertility / IMPC
  • increased mean corpuscular volume / IMPC
  • abnormal cranium morphology / IMPC
MGI phenotypes (gene matching)
  • abnormal female reproductive system morphology / MGI
  • small ovary / MGI
  • abnormal male reproductive system morphology / MGI
  • abnormal testis morphology / MGI
  • small testis / MGI
  • Leydig cell hyperplasia / MGI
  • small seminiferous tubules / MGI
  • increased body weight / MGI
  • decreased body weight / MGI
  • decreased body size / MGI
  • abnormal locomotor behavior / MGI
  • hyperactivity / MGI
  • polydipsia / MGI
  • impaired limb coordination / MGI
  • hyperglycemia / MGI
  • increased urine glucose level / MGI
  • polyuria / MGI
  • reduced male fertility / MGI
  • male infertility / MGI
  • female infertility / MGI
  • abnormal glucose homeostasis / MGI
  • postnatal lethality / MGI
  • abnormal fertility/fecundity / MGI
  • no abnormal phenotype detected / MGI
  • abnormal seminiferous tubule morphology / MGI
  • abnormal corpus luteum morphology / MGI
  • oligozoospermia / MGI
  • decreased circulating insulin level / MGI
  • abnormal Sertoli cell morphology / MGI
  • absent Leydig cells / MGI
  • decreased circulating follicle stimulating hormone level / MGI
  • ketoaciduria / MGI
  • abnormal cell cycle / MGI
  • impaired luteinization / MGI
  • increased pancreatic beta cell number / MGI
  • abnormal male reproductive system physiology / MGI
  • abnormal female reproductive system physiology / MGI
  • decreased testis weight / MGI
  • azoospermia / MGI
  • decreased circulating progesterone level / MGI
  • abnormal pancreatic islet morphology / MGI
  • homeostasis/metabolism phenotype / MGI
  • Leydig cell hypoplasia / MGI
  • decreased lactotroph cell number / MGI
  • adenohypophysis hypoplasia / MGI
  • delayed estrous cycle / MGI
  • small pancreatic islets / MGI
  • postnatal lethality, incomplete penetrance / MGI

Literature references

  • Mice thrive without Cdk4 and Cdk2.;Barrière Cédric, Santamaría David, Cerqueira Antonio, Galán Javier, Martín Alberto, Ortega Sagrario, Malumbres Marcos, Dubus Pierre, Barbacid Mariano, ;2007;Molecular oncology;1;72-83; 19383288
  • A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.;Puyol Marta, Martín Alberto, Dubus Pierre, Mulero Francisca, Pizcueta Pilar, Khan Gulfaraz, Guerra Carmen, Santamaría David, Barbacid Mariano, ;2010;Cancer cell;18;63-73; 20609353

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Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

  • Frozen embryos. Delivered in 4 weeks (after paperwork in place). €1740*
  • Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740*
  • Rederivation of mice from frozen stock, delivery time available upon request . €3880*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

More details on pricing and delivery times

Practical information

Genotyping protocol

Example health report
(Current health report will be provided later)

Material Transfer Agreement (MTA)
Distribution of this strain is subject to a provider MTA. Both signing of the MTA and submission of the online EMMA Mutant Request Form are required before material can be shipped.

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