cardiovascular system phenotype

• abnormal blood vessel morphology
  • delayed regression of vitreal vasculature, however the heart is histologically normal
  (MGI Ref ID J:88367)

immune system phenotype

• abnormal bone marrow development
  • increased replicative senescence in bone marrow stromal stem cells from attenuated cell cycle
  (MGI Ref ID J:94703)

• decreased thymocyte number
  • fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal
  (MGI Ref ID J:36821)

• abnormal osteoclast physiology
  • osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells
  (MGI Ref ID J:94703)

mammalian phenotype

• cellular phenotype
  • Normal - normal phosphatidyl serine flip-flop in thymocytes treated with dexamethasone
  (MGI Ref ID J:59875)
  • Normal - E12.5 primary telencephalic cultures undergo normal cell death in response to AraC treatment
  (MGI Ref ID J:66953)

• immune system phenotype
  • Normal - normal thymocyte expression patterns of CD4, CD8, CD25, CD69, and heat stable antigen
  (MGI Ref ID J:36821)

• renal/urinary system phenotype
  • Normal - kidney is histologically normal
  (MGI Ref ID J:36821)

• respiratory system phenotype
  • Normal - lung is histologically normal
  (MGI Ref ID J:36821)

• nervous system phenotype
  • Normal - normal cell number and apoptotic kinetics within the retinal ganglion cell layer and normal width of the nerve fiber and plexiform layers
  (MGI Ref ID J:88367)

• reproductive system phenotype
  • Normal - testis is histologically normal
  (MGI Ref ID J:36821)

• vision/eye phenotype
  • Normal - normal cell number and apoptotic kinetics within the retinal ganglion cell layer and normal width of the nerve fiber and plexiform layers
  (MGI Ref ID J:88367)

mortality/aging

• postnatal lethality, complete penetrance
  • Background Sensitivity - animals surviving to birth die between 1-3 weeks of age
  (MGI Ref ID J:36821)

• prenatal lethality, incomplete penetrance
  • incomplete penetrance with only 7% homozygous offspring from heterozygote x heterozygote breeders
  (MGI Ref ID J:36821)

nervous system phenotype

• abnormal brain morphology
  • multiple indentations and ectopic cell masses in the cerebrum mantel
  (MGI Ref ID J:36821)
  • protrusion of brain tissue from the skull at the frontal bone area
  (MGI Ref ID J:36821)

• abnormal cerebellum development
  • the germinal layer is thick and mitotically active at P16, at a time when it is normally absent, and spindle-shaped granule cells traverse the molecular layer
  (MGI Ref ID J:36821)

• abnormal forebrain morphology
  • ectopic cell masses are found between the cerebral cortex, the hippocampus and the striatum
  (MGI Ref ID J:36821)

• hydrocephaly
  • diencephalic lumen is frequently obstructed at E17
  (MGI Ref ID J:36821)

• abnormal diencephalon morphology
  • thicker diencephalic wall with supernumerary cell masses is seen at E12
  (MGI Ref ID J:36821)

• abnormal cerebellum external granule cell layer morphology
  • the germinal layer is thick and mitotically active at P16, at a time when it is normally absent
  (MGI Ref ID J:36821)

• abnormal cerebellar granule layer morphology
  • thickness of the internal granular layer is increased
  (MGI Ref ID J:36821)

• abnormal cerebellar molecular layer
  • numerous spindle-shaped granule cells are seen traversing the molecular layer
  (MGI Ref ID J:36821)

• abnormal brainstem morphology
  • increase in cell number and density of the brainstem at E12
  (MGI Ref ID J:36821)

cellular phenotype

• decreased apoptosis
  • pyknotic clusters at sites of major morphogenetic change during brain development are not observed, indicating a decrease in apoptosis in the brain
  (MGI Ref ID J:36821)
  • however, thymocytes show normal susceptibility to apoptosis
  (MGI Ref ID J:36821)

pigmentation phenotype

• abnormal retinal pigment epithelium morphology
  • absence of the retinal pigment epithelium in a region encircling the optic nerve
  (MGI Ref ID J:88367)

skeleton phenotype

• abnormal bone ossification
  • reduced bone volume to tissue volume ratio
  (MGI Ref ID J:94703)
  • reduced trabecular thickness
  (MGI Ref ID J:94703)

• delayed bone ossification
  • evident at E14.5 in skull, metacarpi, phalanges, and sternum and at E17.5 in interparietal bones and metatarsi
  (MGI Ref ID J:94703)

• abnormal sagittal suture morphology
  • open sagittal suture of anterior frontal bone at 7 weeks of age
  (MGI Ref ID J:94703)

• decreased trabecular bone thickness
  (MGI Ref ID J:94703)

• abnormal skeleton development
  • skeleton is smaller than normal at 1 week of age
  (MGI Ref ID J:94703)

• cranioschisis
  • either completely open sagittal suture or incomplete closure at 7 weeks of age
  (MGI Ref ID J:94703)

• abnormal osteoclast physiology
  • osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells
  (MGI Ref ID J:94703)

vision/eye phenotype

• abnormal retina morphology
  • in severe cases, the posterior retina is folded and elevated at the optic nerve head
  (MGI Ref ID J:88367)
  • retinal dysplasia near the optic nerve ranging from absence of retinal pigment epithelium to whorled and folded neuroretina
  (MGI Ref ID J:88367)

• abnormal retinal inner nuclear layer morphology
  • delayed apoptotic kinetics result in thickened inner nuclear layer at 5 days of age which resolves after 13 days of age
  (MGI Ref ID J:88367)

• abnormal retinal pigment epithelium morphology
  • absence of the retinal pigment epithelium in a region encircling the optic nerve
  (MGI Ref ID J:88367)

• abnormal eye morphology
  • protrusions of the neuroepithelium in the retina, causing compression on the lens
  (MGI Ref ID J:36821)

• microphthalmia
  • eyes are 85% to 90% smaller than those of heterozygotes or wild-type
  (MGI Ref ID J:88367)

• abnormal optic stalk morphology
  • optic stalk contains fewer pyknotic cells and is much larger than in wild-type
  (MGI Ref ID J:36821)

• abnormal eye development
  • delayed regression of vitreal vasculature
  (MGI Ref ID J:88367)

craniofacial phenotype

• cranioschisis
  • either completely open sagittal suture or incomplete closure at 7 weeks of age
  (MGI Ref ID J:94703)

• abnormal sagittal suture morphology
  • open sagittal suture of anterior frontal bone at 7 weeks of age
  (MGI Ref ID J:94703)

endocrine/exocrine gland phenotype

• decreased thymocyte number
  • fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal
  (MGI Ref ID J:36821)

growth/size/body region phenotype

• decreased body size
  • smaller than littermates
  (MGI Ref ID J:36821)

hematopoietic system phenotype

• abnormal osteoclast physiology
  • osteoclast activity is reduced, most likely due to dysfunctional preosteoblastic cells
  (MGI Ref ID J:94703)

• decreased thymocyte number
  • fewer total thymocytes at 2 weeks of age, however the spleen is histologically normal
  (MGI Ref ID J:36821)

craniofacial phenotype

• abnormal sagittal suture morphology
  • incomplete closure of sagittal suture of anterior frontal bone at 7 weeks of age
  (MGI Ref ID J:94703)

• cranioschisis
  (MGI Ref ID J:94703)

skeleton phenotype

• abnormal bone ossification
  • reduced bone marrow density
  (MGI Ref ID J:94703)
  • impaired osteogenic differentiation
  (MGI Ref ID J:94703)
  • reduced trabecular thickness at 3 weeks of age
  (MGI Ref ID J:94703)

• abnormal sagittal suture morphology
  • incomplete closure of sagittal suture of anterior frontal bone at 7 weeks of age
  (MGI Ref ID J:94703)

• cranioschisis
  (MGI Ref ID J:94703)

• decreased bone mineral density
  • decreased bone mineral density with age with onset beginning at 3 weeks of age
  (MGI Ref ID J:94703)

• abnormal bone remodeling
  (MGI Ref ID J:94703)

cellular phenotype

• abnormal apoptosis
  • hemorrhagic response and destruction of the hepatic enothelium and subsequent death in response to injection with anti-Fas antibody Jo2 are delayed at least 12 hours relative to that in wildtype mice and the apoptotic pathway aberrently involves activation, but not altered expression, of caspases 2, 6, and 7
  (MGI Ref ID J:65496)
  • n, but not altered expression, of caspases 2, 6, and 7
  (MGI Ref ID J:65496)

• decreased fibroblast apoptosis
  • following UV irradiation and staurosporine treatment, mouse embryonic fibroblasts (MEFs) exhibit increased survival compared to wild type MEFs but not as much as Casp7^tm1Flv MEFs
  (MGI Ref ID J:105496)

• decreased sensitivity to induced cell death
  • mouse embryonic fibroblasts treated to initiate apoptosis fail to exhibit DNA fragmentation
  (MGI Ref ID J:105496)

hearing/vestibular/ear phenotype

• increased or absent threshold for auditory brainstem response
  • at 5 weeks of age no significant waves are detected even at 100 dB
  (MGI Ref ID J:68122)

• abnormal ear morphology
  (MGI Ref ID J:68122)

• abnormal organ of Corti morphology
  • hyperplasia and stratified arrangement of border cells throughout all turns of the cochlea at 2 and 5 weeks of age
  (MGI Ref ID J:68122)
  • the greater epithelial ridge persists at 2 weeks of age throughout all turns of the cochlea
  (MGI Ref ID J:68122)
  • the tunnel of Corti and other pericellular spaces are collapsed at 5 weeks of age
  (MGI Ref ID J:68122)

• cochlear degeneration
  (MGI Ref ID J:68122)

• cochlear outer hair cell degeneration
  • at 5 weeks of age degeneration of outer hair cells is apparent with only 3 rows of outer hair cells present in the apical to middle turn
  (MGI Ref ID J:68122)

• cochlear inner hair cell degeneration
  • at 5 weeks of age degeneration of inner hair cells is apparent with only 1 row of inner hair cells present in the apical to middle turn
  (MGI Ref ID J:68122)

• abnormal outer hair cell stereociliary bundle morphology
  (MGI Ref ID J:68122)

• deafness
  (MGI Ref ID J:68122)

• abnormal auditory brainstem response waveform shape
  • ABR analysis at 2 weeks of age shows atypical waves at all frequencies with sound pressures above 70 dB
  (MGI Ref ID J:68122)

• fused outer hair cell stereocilia
  • at 2 weeks of age there is fusion of stereocilia and at 5 weeks of age all outer hair cell stereocilia are fused at the tips to an unidentified V shaped object
  (MGI Ref ID J:68122)

mammalian phenotype

• reproductive system phenotype
  • Normal - normal oocyte apoptosis
  (MGI Ref ID J:101037)(MGI Ref ID J:70205)
  • Background Sensitivity - normal fertility and viable for more than 6 months
  (MGI Ref ID J:101037)
  • Normal - normal ovarian architecture with normal numbers of nonatretic primordial, primary, and small preantral follicles
  (MGI Ref ID J:101037)

• vision/eye phenotype
  • Normal - the size of the lens organelle free zone is normal
  (MGI Ref ID J:101037)

nervous system phenotype

• abnormal outer hair cell stereociliary bundle morphology
  (MGI Ref ID J:68122)

• cochlear inner hair cell degeneration
  • at 5 weeks of age degeneration of inner hair cells is apparent with only 1 row of inner hair cells present in the apical to middle turn
  (MGI Ref ID J:68122)

• cochlear ganglion degeneration
  • at 5 weeks of age neurons are lost from the basal spiral ganglion
  (MGI Ref ID J:68122)

• cochlear outer hair cell degeneration
  • at 5 weeks of age degeneration of outer hair cells is apparent with only 3 rows of outer hair cells present in the apical to middle turn
  (MGI Ref ID J:68122)

• fused outer hair cell stereocilia
  • at 2 weeks of age there is fusion of stereocilia and at 5 weeks of age all outer hair cell stereocilia are fused at the tips to an unidentified V shaped object
  (MGI Ref ID J:68122)

reproductive system phenotype

• abnormal ovarian follicle morphology
  • shrunken and disorganized atretic follicles lacking blood cell infiltration
  (MGI Ref ID J:70205)

• abnormal granulosa cell morphology
  • granulosa cells of atretic follicles are not eliminated by apoptosis and when cultured in the absence of serum fail to complete nuclear fragmentation after initial DNA condensation
  (MGI Ref ID J:70205)

vision/eye phenotype

• abnormal lens epithelium morphology
  • the epithelium at the anterior lens pole is multilayered and disorganized and the lens capsule above the opaque region has irregular folds
  (MGI Ref ID J:101037)

• cataract
  • marked cataracts on the optic acis due to accumulation of epithelial cells at the anterior pole of the lens evident by the end of the first postnatal week, mature by 3 weeks of age, but most 6 month to 2 year old homozygotes no longer have cataracts
  (MGI Ref ID J:101037)

• abnormal lens development
  • slight reduction in lysis of fluorogenic substrate DEVD-AMC in both the core and cortex of the lens
  (MGI Ref ID J:101037)

endocrine/exocrine gland phenotype

• abnormal ovarian follicle morphology
  • shrunken and disorganized atretic follicles lacking blood cell infiltration
  (MGI Ref ID J:70205)

• abnormal granulosa cell morphology
  • granulosa cells of atretic follicles are not eliminated by apoptosis and when cultured in the absence of serum fail to complete nuclear fragmentation after initial DNA condensation
  (MGI Ref ID J:70205)

cardiovascular system phenotype

• increased cardiomyocyte apoptosis
  • in mice treated with doxorubicin
  (MGI Ref ID J:189241)

muscle phenotype

• increased cardiomyocyte apoptosis
  • in mice treated with doxorubicin
  (MGI Ref ID J:189241)

cellular phenotype

• increased cardiomyocyte apoptosis
  • in mice treated with doxorubicin
  (MGI Ref ID J:189241)

• increased cellular sensitivity to ultraviolet irradiation
  • mice exposed to UV-B radiation exhibit increased cell death (apoptotic and necrosis-like combined) compared with wild-type mice
  (MGI Ref ID J:189241)
  • mice exposed to UV-B radiation exhibit increased keratinocytes undergoing necrosis-like death compared with wild-type mice
  (MGI Ref ID J:189241)
  • mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice
  (MGI Ref ID J:189241)

• decreased keratinocyte apoptosis
  • mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice
  (MGI Ref ID J:189241)

• increased sensitivity to induced cell death
  • in the cardiomyocytes of mice treated with doxorubicin
  (MGI Ref ID J:189241)

integument phenotype

• decreased keratinocyte apoptosis
  • mice exhibit decreased sunburn cells with reduced apoptotic keratinocytes generated by UV-B in the skin compared with wild-type mice
  (MGI Ref ID J:189241)

• abnormal keratinocyte physiology
  • mice exposed to UV-B radiation exhibit increased keratinocytes undergoing necrosis-like death compared with wild-type mice
  (MGI Ref ID J:189241)

mammalian phenotype

• hearing/vestibular/ear phenotype
  • Normal - hearing and cochlear morphology normal
  (MGI Ref ID J:68122)