Phenotypes associated with this allele

• Allele Symbol: Cdk2^tm1Kald
• Allele Name: targeted mutation 1, Philipp Kaldis
• Allele ID: MGI:2679913
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdk2^tm1Kald/Cdk2^tm1Kald	involves: 129S1/Sv	MGI:3818315
hm2	Cdk2^tm1Kald/Cdk2^tm1Kald	involves: 129S1/Sv * C57BL/6	MGI:2679951
cx3	Cdk2^tm1Kald/Cdk2^tm1Kald Cdk4^tm1Kiyo/Cdk4^tm1Kiyo	involves: 129S1/Sv * C57BL/6	MGI:3639608
cx4	Cdk2^tm1Kald/Cdk2^tm1Kald Cdk4^tm1Kiyo/Cdk4^tm1Kiyo Cdkn1b^tm1Ako/Cdkn1b^tm1Ako	involves: 129S1/Sv * C57BL/6	MGI:3639610
cx5	Cdk1^tm1(Cdk2)Kald/Cdk1^+ Cdk2^tm1Kald/Cdk2^tm1Kald	involves: 129S1/Sv * C57BL/6	MGI:3818314

Genotype
MGI:3818315

hm1

• Allelic Composition: Cdk2^tm1Kald/Cdk2^tm1Kald
• Genetic Background: involves: 129S1/Sv

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

reproductive system

abnormal male meiosis ( J:141249 )

♂ • spermatocytes with pachytene morphology and condensed sex body are rarely observed in adult males

infertility ( J:141249 )

liver/biliary system

decreased hepatocyte proliferation ( J:141249 )

• there are reduced numbers of proliferating hepatocytes 24 and 48 hours after partial hepatectomy

• there is also a slight delay in cells entering the S-phase 24 hours after partial hepatectomy

cellular

abnormal male meiosis ( J:141249 )

♂ • spermatocytes with pachytene morphology and condensed sex body are rarely observed in adult males

decreased hepatocyte proliferation ( J:141249 )

• there are reduced numbers of proliferating hepatocytes 24 and 48 hours after partial hepatectomy

• there is also a slight delay in cells entering the S-phase 24 hours after partial hepatectomy

Genotype
MGI:2679951

hm2

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

mortality/aging

preweaning lethality, incomplete penetrance ( J:86203 )

• frequency of homozygous mutant mice was slightly below that expected by Mendelian ratios

• low penetrance

growth/size/body

decreased body size ( J:86203 )

• mice are slightly smaller after weaning than wild-type

reproductive system

abnormal oogenesis ( J:86203 )

♀

absent oocytes ( J:86203 )

♀ • oocytes do not develop in the atrophic ovaries

abnormal ovary morphology ( J:86203 )

♀

absent primordial ovarian follicles ( J:86203 )

♀ • absent primordial follicles in the ovaries

ovary atrophy ( J:86203 )

♀ • severe atrophy

small seminiferous tubules ( J:86203 )

♂ • small seminiferous tubules due to the large depletion of germ cells

small testis ( J:86203 )

♂

uterus atrophy ( J:86203 )

♀

abnormal spermatogenesis ( J:86203 )

♂

azoospermia ( J:86203 )

♂ • post-meiotic cells (late spermatocytes, spermatids, and spermatozoa) are absent

♂ • however, early spermatogonia are present and Sertoli cells are normal

abnormal male meiosis ( J:86203 )

♂ • defective differentiation of male germ cells in males as young as 3 weeks, indicating that germ cells do not enter meiosis

female infertility ( J:86203 )

♀

male infertility ( J:86203 )

♂

endocrine/exocrine glands

abnormal ovary morphology ( J:86203 )

♀

absent primordial ovarian follicles ( J:86203 )

♀ • absent primordial follicles in the ovaries

ovary atrophy ( J:86203 )

♀ • severe atrophy

small seminiferous tubules ( J:86203 )

♂ • small seminiferous tubules due to the large depletion of germ cells

small testis ( J:86203 )

♂

cellular

azoospermia ( J:86203 )

♂ • post-meiotic cells (late spermatocytes, spermatids, and spermatozoa) are absent

♂ • however, early spermatogonia are present and Sertoli cells are normal

abnormal cell cycle ( J:86203 )

• synchronized MEFs show a delay in their entry into S phase by at least 4 hours compared to wild-type MEFs

abnormal male meiosis ( J:86203 )

♂ • defective differentiation of male germ cells in males as young as 3 weeks, indicating that germ cells do not enter meiosis

abnormal oogenesis ( J:86203 )

♀

absent oocytes ( J:86203 )

♀ • oocytes do not develop in the atrophic ovaries

Genotype
MGI:3639608

cx3

• 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

cx4

• 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

Genotype
MGI:3818314

cx5

• Allelic Composition: Cdk1^{tm1(Cdk2)Kald}/Cdk1⁺; Cdk2^tm1Kald/Cdk2^tm1Kald
• Genetic Background: involves: 129S1/Sv * C57BL/6

reproductive system

absent oocytes ( J:141249 )

♀ • oocytes fail to develop in the atrophied ovaries of these mice

increased male germ cell apoptosis ( J:141249 )

♂ • there is extensive apoptosis of male germ cells in 20-day old males

abnormal female reproductive system morphology ( J:141249 )

♀

absent ovarian follicles ( J:141249 )

♀ • no follicles are observed in the ovaries of 90-day old mice

small ovary ( J:141249 )

♀ • ovaries of adult female mice are only half the size of controls

abnormal spermatogenesis ( J:141249 )

♂

abnormal spermatid morphology ( J:141249 )

♂ • round spermatids are absent in the testis of 20-day old males

abnormal spermatocyte morphology ( J:141249 )

♂ • spermatocyte numbers are depleted in the testes of 3-month old mice

♂ • there is an increase in the number of apoptotic spermatocytes in the testes of 10-day old mice

abnormal male meiosis ( J:141249 )

♂ • a greater number of spermatocytes reach the pachytene stage of meiosis than controls

abnormal male reproductive system morphology ( J:141249 )

♂

small seminiferous tubules ( J:141249 )

♂ • the seminiferous tubules are much smaller in 3-month old males

small testis ( J:141249 )

♂ • testis are 20-30% smaller than controls at twenty days of age

♂ • testis of adult males are only half the size of controls

infertility ( J:141249 )

• both male and female mice are sterile

female infertility ( J:141249 )

♀

male infertility ( J:141249 )

♂

endocrine/exocrine glands

absent ovarian follicles ( J:141249 )

♀ • no follicles are observed in the ovaries of 90-day old mice

small ovary ( J:141249 )

♀ • ovaries of adult female mice are only half the size of controls

small seminiferous tubules ( J:141249 )

♂ • the seminiferous tubules are much smaller in 3-month old males

small testis ( J:141249 )

♂ • testis are 20-30% smaller than controls at twenty days of age

♂ • testis of adult males are only half the size of controls

cellular

absent oocytes ( J:141249 )

♀ • oocytes fail to develop in the atrophied ovaries of these mice

abnormal spermatid morphology ( J:141249 )

♂ • round spermatids are absent in the testis of 20-day old males

abnormal spermatocyte morphology ( J:141249 )

♂ • spermatocyte numbers are depleted in the testes of 3-month old mice

♂ • there is an increase in the number of apoptotic spermatocytes in the testes of 10-day old mice

abnormal male meiosis ( J:141249 )

♂ • a greater number of spermatocytes reach the pachytene stage of meiosis than controls

increased male germ cell apoptosis ( J:141249 )

♂ • there is extensive apoptosis of male germ cells in 20-day old males