Phenotypes associated with this allele

• Allele Symbol: Cdk4^tm2.1Bbd
• Allele Name: targeted mutation 2.1, Mariano Barbacid
• Allele ID: MGI:3759558
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844191
cn2	Cdk4^tm2.2Bbd/Cdk4^tm2.1Bbd Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844192
cn3	Cdk2^tm2Sgo/Cdk2^tm2Sgo Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd Polr2a^tm1(cre/ERT2)Bbd/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3759577
cx4	Cdk2^tm1Sgo/Cdk2^tm1Sgo Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL	MGI:3759575
cx5	Cdk2^tm1Sgo/Cdk2^+ Cdk4^tm2.1Bbd/Cdk4^+	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL	MGI:3759576

Genotype
MGI:4844191

cn1

• Allelic Composition: Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd; Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

neoplasm

decreased tumor growth/size ( J:161780 )

• lung cells in tamoxifen-treated mice exhibit 8- to 10-fold reduction in proliferation and early senescence compared to in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

increased adenocarcinoma incidence ( J:161780 )

• tamoxifen-treated mice exhibit adenocarcinomas that are not as severe as in Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

cellular

decreased cell proliferation ( J:161780 )

• proliferation of lung cells in tamoxifen-treated mice exhibit 8- to 10-fold less proliferation than in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

early cellular replicative senescence ( J:161780 )

• tamoxifen-treated mice exhibit increased cell replicative senescence in the lungs compared to in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

Genotype
MGI:4844192

cn2

• Allelic Composition: Cdk4^tm2.2Bbd/Cdk4^tm2.1Bbd; Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

decreased tumor growth/size ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation and early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus

decreased tumor incidence ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit reduced lesions compared to in mice treated with tamoxifen and infected with GFP-expressing adenovirus

increased tumor incidence ( J:161780 )

• in tamoxifen-treated mice as in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

cellular

decreased cell proliferation ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus

early cellular replicative senescence ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus

Genotype
MGI:3759577

cn3

• Allelic Composition: Cdk2^tm2Sgo/Cdk2^tm2Sgo; Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

growth/size/body

decreased body size ( J:125217 )

• when 5 month old mice were treated with tamoxifen they exhibit reduced body size associated with the loss of the Cdk4 function

immune system

increased susceptibility to autoimmune diabetes ( J:125217 )

• when 5 month old mice were treated with tamoxifen they exhibit diabetes associated with the loss of the Cdk4 function

hematopoietic system

hematopoietic system phenotype ( J:125217 )

N • adult hematopoiesis is normal following tamoxifen treatment at 5 months of age

liver/biliary system

liver/biliary system phenotype ( J:125217 )

N • liver regeneration is normal following tamoxifen treatment at 5 months of age

Genotype
MGI:3759575

cx4

• Allelic Composition: Cdk2^tm1Sgo/Cdk2^tm1Sgo; Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:125217 )

• although mice move and ingest milk at birth, they die within 24 hours due to cardiac failure

cardiovascular system

increased myocardial fiber size ( J:125217 )

• in some cases cardiomyocytes are hypertrophic and are partially disorganized by prominent capillaries

thin ventricular wall ( J:125217 )

• thin ventricular walls are associated with a one-third decrease in the number of proliferating cardiomyocytes

abnormal fetal cardiomyocyte proliferation ( J:125217 )

• thin ventricular walls are associated with a one-third decrease in the number of proliferating cardiomyocytes

congestive heart failure ( J:125217 )

• mice die within 24 hours of birth due to cardiac failure

liver/biliary system

liver hypoplasia ( J:125217 )

• fetal livers contain 60% of the cells found in wild-type livers

• however, this reduction is proportional to the reduction in overall size of embryos

• the number of hematopoietic cells in the fetal liver is reduced compared to in wild-type mice

abnormal liver physiology ( J:125217 )

• mice suffer from congestive livers

hematopoietic system

abnormal definitive hematopoiesis ( J:125217 )

• the number of hematopoietic cells in the fetal liver is reduced compared to in wild-type mice

• however, the number of granulocyte-macrophage progenitors, common myeloid progenitors and megakaryocyte-erythroid progenitor cells are normal

decreased erythrocyte cell number ( J:125217 )

• at E17.5, mice have a small decrease in red blood cell (RBC) number (1.27x10⁶+/-0.14 RBC per mm³ compared to 1.45x10⁶+/-0.11 RBC per mm³ in wild-type mice)

• however, this decrease does not affect viability

cellular

abnormal fetal cardiomyocyte proliferation ( J:125217 )

• thin ventricular walls are associated with a one-third decrease in the number of proliferating cardiomyocytes

abnormal cell cycle ( J:125217 )

• primary mouse embryonic fibroblast cells are delayed in the percent of cells entering into S phase but eventually equalize with wild-type cells

decreased fibroblast proliferation ( J:125217 )

• proliferation of mouse embryonic fibroblast (MEF) cells is decreased relative to wild-type MEFs

growth/size/body

decreased body weight ( J:125217 )

• at birth mice weigh 25% to 40% less than wild-type mice

muscle

increased myocardial fiber size ( J:125217 )

• in some cases cardiomyocytes are hypertrophic and are partially disorganized by prominent capillaries

abnormal fetal cardiomyocyte proliferation ( J:125217 )

• thin ventricular walls are associated with a one-third decrease in the number of proliferating cardiomyocytes

Genotype
MGI:3759576

cx5

• Allelic Composition: Cdk2^tm1Sgo/Cdk2⁺; Cdk4^tm2.1Bbd/Cdk4⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6 * SJL

embryo

abnormal embryo development ( J:125217 )

• 60% of mice do not complete embryonic development