Phenotypes associated with this allele

• Allele Symbol: Cdk4^tm1Kiyo
• Allele Name: targeted mutation 1, Hiroaki Kiyokawa
• Allele ID: MGI:2149587
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdk4^tm1Kiyo/Cdk4^tm1Kiyo	involves: 129S1/Sv	MGI:3712954
hm2	Cdk4^tm1Kiyo/Cdk4^tm1Kiyo	involves: 129S1/Sv * C57BL/6	MGI:2174939
cx3	Cdk4^tm1Kiyo/Cdk4^tm1Kiyo Lin9^tm1Orc/Lin9^tm1Orc	involves: 129S1/Sv	MGI:3712953
cx4	Cdk4^tm1Kiyo/Cdk4^+ Lin9^tm1Orc/Lin9^+	involves: 129S1/Sv	MGI:3712956
cx5	Cdk2^tm1Kald/Cdk2^tm1Kald Cdk4^tm1Kiyo/Cdk4^tm1Kiyo	involves: 129S1/Sv * C57BL/6	MGI:3639608
cx6	Cdk2^tm1Kald/Cdk2^tm1Kald Cdk4^tm1Kiyo/Cdk4^tm1Kiyo Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * C57BL/6	MGI:3639610

Genotype
MGI:3712954

hm1

• Allelic Composition: Cdk4^tm1Kiyo/Cdk4^tm1Kiyo
• Genetic Background: involves: 129S1/Sv

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

reproductive system

azoospermia ( J:111333 )

♂ • no sperm are detected in the epididiymis

absent Leydig cells ( J:111333 )

♂

female infertility ( J:111333 )

♀ • 100% of females are infertile

male infertility ( J:111333 )

♂ • 6 of 7 mice are infertile with the remaining mice becoming infertile after 2 to 3 months

endocrine/exocrine glands

decreased lactotroph cell number ( J:111333 )

• decrease in pituitary lactotrophs

adenohypophysis hypoplasia ( J:111333 )

• anterior pituitary cellularity is reduced (2.4x10⁵ compared to 2.2x10⁶ in wild-type mice)

absent Leydig cells ( J:111333 )

♂

growth/size/body

decreased body weight ( J:111333 )

nervous system

decreased lactotroph cell number ( J:111333 )

• decrease in pituitary lactotrophs

adenohypophysis hypoplasia ( J:111333 )

• anterior pituitary cellularity is reduced (2.4x10⁵ compared to 2.2x10⁶ in wild-type mice)

cellular

azoospermia ( J:111333 )

♂ • no sperm are detected in the epididiymis

Genotype
MGI:2174939

hm2

• Allelic Composition: Cdk4^tm1Kiyo/Cdk4^tm1Kiyo
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:57854 )

• 22% of homozygous mutant mice died by 28 days after birth

growth/size/body

decreased body size ( J:57854 )

• at birth, homozygous mutant mice were 20% smaller than wild-type or heterozygous littermates

• adult homozygous mutant mice were approximately 42% smaller than wild-type or heterozygous littermates

reproductive system

oligozoospermia ( J:57854 )

♂ • reduced numbers of spermatogonia/spermatocytes

abnormal female reproductive system morphology ( J:57854 )

♀

abnormal corpus luteum morphology ( J:57854 )

♀ • perturbation of organization of granulosa/luteal cells

abnormal male reproductive system morphology ( J:57854 )

♂

abnormal testis morphology ( J:57854 )

♂ • testicular dysplasia

small seminiferous tubules ( J:57854 )

♂ • reduced diameter of seminiferous epithelial tubules

small testis ( J:57854 )

♂

impaired luteinization ( J:57854 )

♀ • aberrant luteinization, with oocytes trapped

abnormal fertility/fecundity ( J:57854 )

female infertility ( J:57854 )

♀ • all females infertile

reduced male fertility ( J:57854 )

♂ • only 10% of males fertile

homeostasis/metabolism

increased urine glucose level ( J:57854 )

• by 6 to 7 weeks, 60 - 80% of homozygous mutant mice started exhibiting glucosuria; remaining mice showed no such phenotype up to 40 weeks

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:57854 )

• degeneration of endocrine islet cells

• at 3 weeks of age, pancreas had fewer islets, many of which had disorganized cellularity and dying cells with condensed nuclei

abnormal corpus luteum morphology ( J:57854 )

♀ • perturbation of organization of granulosa/luteal cells

abnormal testis morphology ( J:57854 )

♂ • testicular dysplasia

small seminiferous tubules ( J:57854 )

♂ • reduced diameter of seminiferous epithelial tubules

small testis ( J:57854 )

♂

renal/urinary system

increased urine glucose level ( J:57854 )

• by 6 to 7 weeks, 60 - 80% of homozygous mutant mice started exhibiting glucosuria; remaining mice showed no such phenotype up to 40 weeks

cellular

oligozoospermia ( J:57854 )

♂ • reduced numbers of spermatogonia/spermatocytes

Genotype
MGI:3712953

cx3

• Allelic Composition: Cdk4^tm1Kiyo/Cdk4^tm1Kiyo; Lin9^tm1Orc/Lin9^tm1Orc
• Genetic Background: involves: 129S1/Sv

reproductive system

female infertility ( J:111333 )

♀ • 50% of females are infertile

male infertility ( J:111333 )

♂ • 10% of mice are infertile

endocrine/exocrine glands

adenohypophysis hypoplasia ( J:111333 )

• anterior pituitary cellularity is reduced (2.7x10⁵ compared to 2.2x10⁶ in wild-type mice)

growth/size/body

decreased body weight ( J:111333 )

• mice are smaller than normal but larger than Cdk4^tm1Kiyo homozygotes

cellular

abnormal cell cycle ( J:111333 )

• number of MEF cells in S-phase is increased by almost 5-fold

nervous system

adenohypophysis hypoplasia ( J:111333 )

• anterior pituitary cellularity is reduced (2.7x10⁵ compared to 2.2x10⁶ in wild-type mice)

Genotype
MGI:3712956

cx4

• Allelic Composition: Cdk4^tm1Kiyo/Cdk4⁺; Lin9^tm1Orc/Lin9⁺
• Genetic Background: involves: 129S1/Sv

cellular

abnormal cell cycle ( J:111333 )

• number of MEF cells in S-phase is increased by 2.3-fold

immune system

decreased susceptibility to autoimmune diabetes ( J:111333 )

• mice do not develop early onset diabetes

Genotype
MGI:3639608

cx5

• Allelic Composition: Cdk2^tm1Kald/Cdk2^tm1Kald; Cdk4^tm1Kiyo/Cdk4^tm1Kiyo
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:108720 )

• most, but not all, die between E14.5 and E16.5

cardiovascular system

myocardial fiber disarray ( J:108720 )

• cardiomyocytes are hypertrophic and disorganized

increased heart atrium size ( J:108720 )

• enlargement of the atria

ventricular septal defect ( J:108720 )

• partial penetrance of an interventricular septum with a ventricular septal defect

small heart ( J:108720 )

• seen at E14.5

abnormal heart valve morphology ( J:108720 )

• hypertrophy of valves

thin ventricular wall ( J:108720 )

abnormal cardiac output ( J:108720 )

• cardiac output failure

hemorrhage ( J:108720 )

abnormal fetal cardiomyocyte proliferation ( J:108720 )

• proliferation in certain areas of the heart is decreased

cellular

abnormal fetal cardiomyocyte proliferation ( J:108720 )

• proliferation in certain areas of the heart is decreased

abnormal cell cycle ( J:108720 )

• MEFs exhibit impaired S phase entry and premature senescence

decreased cell proliferation ( J:108720 )

• MEFs show decreased proliferation rate

embryo

decreased embryo size ( J:108720 )

• 80% of E14.5 and E15.5 embryos are small

growth/size/body

decreased embryo size ( J:108720 )

• 80% of E14.5 and E15.5 embryos are small

hematopoietic system

abnormal erythrocyte morphology ( J:108720 )

• most nucleated erythroid cells are larger than in wild-type

abnormal hematopoietic stem cell morphology ( J:108720 )

• hematopoietic cells are able to generate all progenitors and mature cells from hematopoietic stem cells, but do so to a lesser extent than wild-type due to reduced proliferation of the multipotential progenitors

homeostasis/metabolism

edema ( J:108720 )

• 14% develop hemorrhagic edema

liver/biliary system

abnormal liver morphology ( J:108720 )

• cellularity is reduced 2.4-fold in fetal livers

muscle

myocardial fiber disarray ( J:108720 )

• cardiomyocytes are hypertrophic and disorganized

abnormal fetal cardiomyocyte proliferation ( J:108720 )

• proliferation in certain areas of the heart is decreased

vision/eye

abnormal eye morphology ( J:108720 )

• 11% exhibit asymmetric ocular lesions

integument

pallor ( J:108720 )

• 26% are pale in color

Genotype
MGI:3639610

cx6

• Allelic Composition: Cdk2^tm1Kald/Cdk2^tm1Kald; Cdk4^tm1Kiyo/Cdk4^tm1Kiyo; Cdkn1b^tm1Ako/Cdkn1b^tm1Ako
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:108720 )

• embryos appear normal at E13.5 and die around E15.5

cellular

decreased cell proliferation ( J:108720 )

• MEFs show decreased proliferation rate