Mouse Genome Informatics
hm1
    Cdk4tm1Bbd/Cdk4tm1Bbd
involves: 129S1/Sv * 129X1/SvJ * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:54534)
(J:54534)
• severe reduction in spermatozoa in older males (J:54534)
• in males with limited fertility, reduced numbers of spermatids and mature sperm cells were evident (J:54534)
• degeneration of primary spermatocytes (J:54534)
• reduced numbers of Leydig cells with numerous apoptotic bodies (J:54534)
• vacuolized Sertoli-cell cytoplasm (J:54534)
• 75% reduction in size and weight of testes compared to controls (J:54534)
• moderately delayed estrous cycles (J:54534)
• infertile, failed to reproduce with wild-type males (J:54534)
• most sterile, 80% failed to induce pregnancy (J:54534)
• males that did produce offspring had small litters (3 - 6 pups) and reproduced only for a short period (2 - 3 months of age) (J:54534)

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 (J:54534)
(J:54534)
• degeneration of primary spermatocytes (J:54534)
• reduced numbers of Leydig cells with numerous apoptotic bodies (J:54534)
• vacuolized Sertoli-cell cytoplasm (J:54534)
• 75% reduction in size and weight of testes compared to controls (J:54534)

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


Mouse Genome Informatics
cx2
    Cdk2tm1Sgo/Cdk2tm1Sgo
Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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


Mouse Genome Informatics
cx3
    Cdk4tm1Bbd/Cdk4tm1Bbd
Cdk6tm1Bbd/Cdk6tm1Bbd

involves: 129S1/Sv * 129X1/SvJ * CD-1 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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
• RBCs are megaloblastic in appearance
• decreased peripheral RBC counts
• 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
• hematopoietic stem cell numbers reduced in proportion to reduced cellularity

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