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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Cdk4tm1Bbd
targeted mutation 1, Mariano Barbacid
MGI:2154520
Summary 3 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Cdk4tm1Bbd/Cdk4tm1Bbd involves: 129S1/Sv * 129X1/SvJ * ICR MGI:2386959
cx2
Cdk2tm1Sgo/Cdk2tm1Sgo
Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:3723204
cx3
Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd
involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR MGI:3054097


Genotype
MGI:2386959
hm1
Allelic
Composition
Cdk4tm1Bbd/Cdk4tm1Bbd
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * ICR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdk4tm1Bbd mutation (0 available); any Cdk4 mutation (37 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• slightly lower ratio of homozygotes produced from heterozygote matings (19.6%)

growth/size/body
• smaller size noticeable at birth and progressively more noticeable with age
• overall reduction in size of all major organs
• adults were 50% the weight of wild-type and heterozygous controls

cellular
• serum-starved fibroblasts derived from mutant mice exhibited a delay in reaching S phase when placed in a rich environment

homeostasis/metabolism
• in adult mice
• females had low circulating levels of follicle-stimulating hormone
• adult mice showed hypoinsulinemia
• females had low circulating levels of progesterone
• high glucose concentrations in urine
• ketone bodies in urine

reproductive system
• defect in corpus luteum formation
• severe reduction in spermatozoa in older males
• in males with limited fertility, reduced numbers of spermatids and mature sperm cells were evident
• degeneration of primary spermatocytes
• reduced numbers of Leydig cells with numerous apoptotic bodies
• vacuolized Sertoli-cell cytoplasm
• 75% reduction in size and weight of testes compared to controls
• moderately delayed estrous cycles
• infertile, failed to reproduce with wild-type males
• most sterile, 80% failed to induce pregnancy
• males that did produce offspring had small litters (3 - 6 pups) and reproduced only for a short period (2 - 3 months of age)

behavior/neurological
• impaired locomotion

renal/urinary system
• high glucose concentrations in urine
• ketone bodies in urine

endocrine/exocrine glands
• mice 2 months of age or older showed severe deformity and reduction in the size of the islets of the pancreas
• defect in corpus luteum formation
• degeneration of primary spermatocytes
• reduced numbers of Leydig cells with numerous apoptotic bodies
• vacuolized Sertoli-cell cytoplasm
• 75% reduction in size and weight of testes compared to controls

Mouse Models of Human Disease
OMIM ID Ref(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:54534




Genotype
MGI:3723204
cx2
Allelic
Composition
Cdk2tm1Sgo/Cdk2tm1Sgo
Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdk2tm1Sgo mutation (1 available); any Cdk2 mutation (9 available)
Cdk4tm1Bbd mutation (0 available); any Cdk4 mutation (37 available)
Cdk6tm1Bbd mutation (1 available); any Cdk6 mutation (16 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice begin to die around E13.5 and all are dying by E15.5
• mice begin to die around E13.5 and all are dying by E15.5

growth/size/body
• between E12.5 and E13.5, embryos are 25% to 40% smaller than wild-type mice

cardiovascular system
• the number of proliferating cardiomyocytes is decreased resulting in thin ventricular walls
• ventricular walls are thinner than in wild-type mice due to a decrease in the number of proliferating cardiomyocytes

cellular
• proliferation of mouse embryonic fibroblast cells is partially compromised
• exiting quiescence following serum treatment is delayed

liver/biliary system
• between E12.5 and E13.5, livers exhibit a three-fold reduction in cellularity that is not accounted for by the decrease in embryo size

hematopoietic system
• common myeloid progenitor cells are reduced 8-fold in number

muscle
• the number of proliferating cardiomyocytes is decreased resulting in thin ventricular walls

embryogenesis
• between E12.5 and E13.5, embryos are 25% to 40% smaller than wild-type mice




Genotype
MGI:3054097
cx3
Allelic
Composition
Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdk4tm1Bbd mutation (0 available); any Cdk4 mutation (37 available)
Cdk6tm1Bbd mutation (1 available); any Cdk6 mutation (16 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• of the few homozygotes to be born alive, all were dead within a few hours of birth
• 25% of homozygotes are dead by E14.5
• 50% dead by E18.5

embryogenesis
• embryos well formed but small

growth/size/body
• embryos well formed but small

hematopoietic system
• decreased numbers of erythroid precursors in the liver and few in proliferative stage
• lymphoid and myeloid lineage reductions are disproportionate
• proliferative potential of all stem cells is severely reduced
• RBCs are megaloblastic in appearance
• decreased peripheral RBC counts
• hematopoietic stem cell numbers reduced in proportion to reduced cellularity

liver/biliary system
• small livers with significantly reduced cellularity by E15.5





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last database update
04/26/2016
MGI 6.03
The Jackson Laboratory