Phenotypes for Cdk4 MGI:2386959 MGI Mouse

mortality/aging

postnatal lethality ( J:54534 )

• slightly lower ratio of homozygotes produced from heterozygote matings (19.6%)

growth/size/body

decreased body size ( J:54534 )

• smaller size noticeable at birth and progressively more noticeable with age

• overall reduction in size of all major organs

decreased body weight ( J:54534 )

• adults were 50% the weight of wild-type and heterozygous controls

cellular

oligozoospermia ( J:54534 )

• severe reduction in spermatozoa in older males

• in males with limited fertility, reduced numbers of spermatids and mature sperm cells were evident

abnormal cell cycle ( J:54534 )

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

homeostasis/metabolism

hyperglycemia ( J:54534 )

• in adult mice

decreased circulating follicle stimulating hormone level ( J:54534 )

• females had low circulating levels of follicle-stimulating hormone

decreased circulating insulin level ( J:54534 )

• adult mice showed hypoinsulinemia

decreased circulating progesterone level ( J:54534 )

• females had low circulating levels of progesterone

increased urine glucose level ( J:54534 )

• high glucose concentrations in urine

ketoaciduria ( J:54534 )

• ketone bodies in urine

reproductive system

oligozoospermia ( J:54534 )

• severe reduction in spermatozoa in older males

• in males with limited fertility, reduced numbers of spermatids and mature sperm cells were evident

abnormal female reproductive system morphology ( J:54534 )

abnormal corpus luteum morphology ( J:54534 )

• defect in corpus luteum formation

small ovary ( J:54534 )

abnormal male reproductive system morphology ( J:54534 )

abnormal seminiferous tubule morphology ( J:54534 )

• degeneration of primary spermatocytes

abnormal Sertoli cell morphology ( J:54534 )

• vacuolized Sertoli-cell cytoplasm

decreased Leydig cell number ( J:54534 )

• reduced numbers of Leydig cells with numerous apoptotic bodies

decreased testis weight ( J:54534 )

• 75% reduction in size and weight of testes compared to controls

abnormal female reproductive system physiology ( J:54534 )

delayed estrus ( J:54534 )

• moderate delay in passing through estrus

female infertility ( J:54534 )

• infertile, failed to reproduce with wild-type males

abnormal male reproductive system physiology ( J:54534 )

reduced male fertility ( J:54534 )

• 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

polydipsia ( J:54534 )

abnormal locomotor behavior ( J:54534 )

• impaired locomotion

impaired limb coordination ( J:54534 )

• staggering

hyperactivity ( J:54534 )

renal/urinary system