All Phenotypes Bmi1<tm1Brn> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bmi1^tm1Brn/Bmi1^tm1Brn	either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB)	MGI:2658682
hm2	Bmi1^tm1Brn/Bmi1^tm1Brn	involves: 129P2/OlaHsd	MGI:2674270
hm3	Bmi1^tm1Brn/Bmi1^tm1Brn	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:6850619
ht4	Bmi1^tm1Brn/Bmi1⁺	involves: 129P2/OlaHsd	MGI:2674271
cn5	Bmi1^tm1Brn/Bmi1^tm1Brn Apc^tm2Cip/Apc⁺ Cdkn2a^tm1Cjs/Cdkn2a^tm1Cjs Tg(Vil1-cre)20Syr/0	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * DBA/2	MGI:5532576
cn6	Bmi1^tm1Brn/Bmi1^tm1Brn Apc^tm2Cip/Apc⁺ Tg(Vil1-cre)20Syr/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:5532574
cx7	Bmi1^tm1Brn/Bmi1^tm1Brn Rnf2^tm1Mvl/Rnf2⁺	involves: 129/Ola * FVB	MGI:3852545
cx8	Pcgf2^tm1Hko/Pcgf2^tm1Hko Bmi1^tm1Brn/Bmi1⁺	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3577617
cx9	Pcgf2^tm1Hko/Pcgf2⁺ Bmi1^tm1Brn/Bmi1^tm1Brn	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3577618
cx10	Pcgf2^tm1Hko/Pcgf2^tm1Hko Bmi1^tm1Brn/Bmi1^tm1Brn	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3577619
cx11	Bmi1^tm1Brn/Bmi1^tm1Brn E2f6^tm1Lees/E2f6⁺	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3790813
cx12	Bmi1^tm1Brn/Bmi1^tm1Brn E2f6^tm1Lees/E2f6^tm1Lees	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3790810
cx13	Bmi1^tm1Brn/Bmi1⁺ E2f6^tm1Lees/E2f6^tm1Lees	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3790811
cx14	Bmi1^tm1Brn/Bmi1⁺ E2f6^tm1Lees/E2f6⁺	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6	MGI:3790812

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn
Genetic Background	either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB)

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)

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

mortality/aging

premature death ( J:17712 )

• animals die between 3-20 weeks of age from repeated illnesses

postnatal lethality, incomplete penetrance ( J:17712 )

• about 50% of animals die between postnatal days 1-3; pups are selectively cannibalized by their mothers

behavior/neurological

tremors ( J:17712 )

ataxia ( J:17712 )

• ataxic gait is first noticeable at 2-4 weeks of age and becomes progressively more severe with age

• walking is uncoordinated and mice fall over onto their side frequently

sporadic seizures ( J:17712 )

growth/size/body

decreased body size ( J:17712 )

• mice that survive the first few days after birth are smaller

hematopoietic system

decreased splenocyte proliferation ( J:17712 )

• proliferative response of adult, but not newborn, splenocytes to LPS or ConA stimulation is reduced 8-10-fold compared to wild-type

thymus cortex hypoplasia ( J:17712 )

decreased thymocyte number ( J:17712 )

• number of thymocytes is decreased to less than 1% of wild-type

abnormal thymus involution ( J:17712 )

• involuted thymus

abnormal definitive hematopoiesis ( J:17712 )

• hematopoieisis is severely reduced

• hematopoietic cell counts are reduced to about 30% of wild-type levels

decreased immature B cell number ( J:17712 )

• absolute number of immature B cells (B220+HSA+ and B220+BPl+) is significantly reduced

abnormal double-negative T cell morphology ( J:17712 )

• the immature CD4-CD8- thymocyte population is increased from 4% of total cells in wild-type to 90% of total cells in mutants, although in absolute numbers, this population size is decreased to 12% of wild-type, indicating the presence of mainly immature thymocytes

anemia ( J:17712 )

• moribund mice exhibit anemia

abnormal bone marrow cell morphology/development ( J:17712 )

• in colony assays, bone marrow cells do not respond to IL-7 or to LPS

• in colony assays, the number of myeloid colonies induced by L-cell-conditioned medium containing M-CSF, is reduced 4-10 fold

• decrease in cell numbers and replacement of large areas of hematopoiesis by adipoctyes in the bone marrow

decreased mature B cell number ( J:17712 )

• number of mature B cells (B220+sIg+) is significantly reduced

abnormal spleen red pulp morphology ( J:17712 )

• hypoplasia of the red pulp

small spleen ( J:17712 )

abnormal spleen white pulp morphology ( J:17712 )

• hypoplasia of the white pulp

decreased IgM level ( J:17712 )

• serum IgM levels are reduced to 70% of wild-type levels

immune system

decreased splenocyte proliferation ( J:17712 )

• proliferative response of adult, but not newborn, splenocytes to LPS or ConA stimulation is reduced 8-10-fold compared to wild-type

thymus cortex hypoplasia ( J:17712 )

decreased thymocyte number ( J:17712 )

• number of thymocytes is decreased to less than 1% of wild-type

abnormal thymus involution ( J:17712 )

• involuted thymus

decreased immature B cell number ( J:17712 )

• absolute number of immature B cells (B220+HSA+ and B220+BPl+) is significantly reduced

abnormal double-negative T cell morphology ( J:17712 )

decreased mature B cell number ( J:17712 )

• number of mature B cells (B220+sIg+) is significantly reduced

abnormal spleen red pulp morphology ( J:17712 )

• hypoplasia of the red pulp

small spleen ( J:17712 )

abnormal spleen white pulp morphology ( J:17712 )

• hypoplasia of the white pulp

decreased IgM level ( J:17712 )

• serum IgM levels are reduced to 70% of wild-type levels

lung inflammation ( J:17712 )

• moribound mice exhibit pneumonia

skeleton

abnormal vertebral arch morphology ( J:17712 )

• broadening and splitting of the neural arch of the atlas or the axis

vertebral transformation ( J:17712 )

• skeletal transformations affecting vertebrae; incomplete penetrance, although each mutant has at least one transformation and 87% have multiple transformations

thoracic vertebral transformation ( J:17712 )

• transformation of T7 to T8, resulting in the presence of six vertebrosternal ribs instead of seven in controls

• transformation of T13 to the first lumbar vertebra (L1), as evidenced by the absence or degeneration of the ribs normally associated with T13

cervical vertebral transformation ( J:17712 )

• transformation of the seventh cervical vertebra (C7) to the first thoracic vertebra (T1), as evidenced by the presence of ribs at C7, which fuse on the ventral side with the ribs associated with T1

lumbar vertebral transformation ( J:17712 )

• transformation of L6 to the first sacral vertebra (S1), as evidenced by the association of the ilial bones with L6 instead of S1 as in controls

nervous system

sporadic seizures ( J:17712 )

abnormal corpus callosum morphology ( J:17712 )

• extensive gliosis

hippocampal neuron degeneration ( J:17712 )

• dark shrunken and degenerating neurons are seen in some mutants

abnormal cerebellar layer morphology ( J:17712 )

• reduced thickness of cerebellar layers, neuron loss

abnormal Purkinje cell morphology ( J:17712 )

• shrunken Purkinje cells

decreased Purkinje cell number ( J:17712 )

thin cerebellar molecular layer ( J:17712 )

gliosis ( J:17712 )

• major white matter tracts, such as the corpus callosum, show extensive gliosis

respiratory system

lung inflammation ( J:17712 )

• moribound mice exhibit pneumonia

cellular

decreased splenocyte proliferation ( J:17712 )

• proliferative response of adult, but not newborn, splenocytes to LPS or ConA stimulation is reduced 8-10-fold compared to wild-type

endocrine/exocrine glands

thymus cortex hypoplasia ( J:17712 )

decreased thymocyte number ( J:17712 )

• number of thymocytes is decreased to less than 1% of wild-type

abnormal thymus involution ( J:17712 )

• involuted thymus

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)

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

mortality/aging

premature death ( J:134271 )

• lethality is seen between 3 and 20 weeks of age

postnatal lethality, incomplete penetrance ( J:134271 )

• about half as many mice as expected are present at weaning however no reduction in numbers is detected at E18.5

growth/size/body

postnatal growth retardation ( J:134271 )

skeleton

abnormal vertebrae morphology ( J:134271 )

• small extra bone present above C1 in 29% of homozygous mice

thoracic vertebral transformation ( J:134271 )

• transformation of T7 to T8 and T13 to L1 are seen in 71% and 57% of homozygous mice, respectively

cervical vertebral transformation ( J:134271 )

• transformation of C1 to C2 and C7 to T1 are seen in 57% and 29% of homozygous mice, respectively

• partial transformation of C7 to T1 is seen in 43% of homozygous mice

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 86% of homozygous mice

hematopoietic system

anemia ( J:134271 )

• severe

abnormal bone marrow cell morphology/development ( J:134271 )

• shift in the distribution of myeloid to B lymphoid cells resulting in an increased percentage of myeloid cells

• within the B cell population, loss of immature B cells is greater than the loss of mature B cells

decreased bone marrow cell number ( J:134271 )

decreased hematopoietic cell number ( J:134271 )

• decreased number of hematopoietic cells in the thymus, bone marrow and spleen

decreased double-positive T cell number ( J:134271 )

reproductive system

teratozoospermia ( J:286451 )

• over 50% of sperm exhibit severe malformations at 7 weeks of age

abnormal sperm mitochondrial sheath morphology ( J:286451 )

• mitochondrial contents are significantly reduced in the sperm mitochondrial sheath

abnormal sperm head morphology ( J:286451 )

• numerous sperm head defects are observed, including irregular, sharp and big heads

• several genes required for sperm shaping are significantly downregulated

detached acrosome ( J:286451 )

• sperm nucleus is detached from the acrosome

abnormal sperm nucleus morphology ( J:286451 )

• sperm exhibit nuclear condensation defects

enlarged sperm head ( J:286451 )

decreased male germ cell number ( J:286451 )

• germ cell counts are reduced in the seminiferous tubule epithelium at 7 weeks of age

oligozoospermia ( J:286451 )

• CASA analysis of sperm counts in caudal epididymis revealed severe oligospermia at 7 weeks of age

abnormal male germ cell physiology ( J:286451 )

• male germ cell proliferation is severely reduced, as determined by Ki67 immunostaining in testicular sections

increased male germ cell apoptosis ( J:286451 )

• male germ cell apoptosis is markedly increased, as determined by a TUNEL assay in testicular sections

abnormal seminiferous tubule epithelium morphology ( J:286451 )

• seminiferous tubule epithelium is highly disorganized at 7 weeks of age

small seminiferous tubules ( J:286451 )

• seminiferous tubule diameters are reduced at 7 weeks of age

decreased Leydig cell number ( J:286451 )

• Leydig cell population (3betaHSD positive cells) is significantly reduced at 7 weeks of age

small testis ( J:286451 )

• testis size is significantly smaller than that in wild-type controls at 7 weeks of age

decreased testis weight ( J:286451 )

• testis weight is significantly reduced at 7 weeks of age

abnormal testis physiology ( J:286451 )

• both p16 and p53 immunopositive cells in testis are significantly increased and the protein expression levels of p16, p19, p53 and p21 are markedly up-regulated in testis extracts from 7-week-old male mice

• reactive oxygen species (ROS) and (H₂O₂) levels are significantly increased whereas total antioxidant capacity and the expression levels of antioxidant enzyme genes (Gpx1, Gsr, Cat, Txnrd1) are decreased

• numbers of 8-OHdG positive cells and gammaH2AX positive cells are dramatically increased in testicular sections, indicating increased DNA damage

decreased testes secretion ( J:286451 )

• testosterone production is reduced and both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice

abnormal epididymis morphology ( J:286451 )

• round immature germ cell like cells are found in epididymal sections at 7 weeks of age

male infertility ( J:286451 )

• male mice mated with adult wild-type females of proven fertility for 1 month are unable to produce offspring, indicating complete male sterility

cellular

teratozoospermia ( J:286451 )

• over 50% of sperm exhibit severe malformations at 7 weeks of age

abnormal sperm mitochondrial sheath morphology ( J:286451 )

• mitochondrial contents are significantly reduced in the sperm mitochondrial sheath

abnormal sperm head morphology ( J:286451 )

• numerous sperm head defects are observed, including irregular, sharp and big heads

• several genes required for sperm shaping are significantly downregulated

detached acrosome ( J:286451 )

• sperm nucleus is detached from the acrosome

abnormal sperm nucleus morphology ( J:286451 )

• sperm exhibit nuclear condensation defects

enlarged sperm head ( J:286451 )

decreased male germ cell number ( J:286451 )

• germ cell counts are reduced in the seminiferous tubule epithelium at 7 weeks of age

oligozoospermia ( J:286451 )

• CASA analysis of sperm counts in caudal epididymis revealed severe oligospermia at 7 weeks of age

abnormal cell cycle ( J:134271 )

• impaired ability of serum-starved MEFs to re-enter the cell cycle

decreased cell proliferation ( J:134271 )

• defect in asynchronous proliferation in MEFs

early cellular replicative senescence ( J:134271 , J:198334 )

• in MEFs (J:134271)

• in mouse embryonic fibroblasts by passage 6 (J:198334)

abnormal male germ cell physiology ( J:286451 )

• male germ cell proliferation is severely reduced, as determined by Ki67 immunostaining in testicular sections

increased male germ cell apoptosis ( J:286451 )

• male germ cell apoptosis is markedly increased, as determined by a TUNEL assay in testicular sections

oxidative stress ( J:286451 )

• reactive oxygen species (ROS) and hydrogen peroxide (H₂O₂) levels are significantly increased whereas total antioxidant capacity and the expression levels of antioxidant enzyme genes (Gpx1, Gsr, Cat, Txnrd1) are decreased in testis extracts from 7-week-old male mice

behavior/neurological

ataxia ( J:134271 )

• seen in mice that survive to 2 months of age

nervous system

cerebellum hypoplasia ( J:134271 )

• all three layers are affected

immune system

decreased double-positive T cell number ( J:134271 )

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:286451 )

• seminiferous tubule epithelium is highly disorganized at 7 weeks of age

small seminiferous tubules ( J:286451 )

• seminiferous tubule diameters are reduced at 7 weeks of age

decreased Leydig cell number ( J:286451 )

• Leydig cell population (3betaHSD positive cells) is significantly reduced at 7 weeks of age

small testis ( J:286451 )

• testis size is significantly smaller than that in wild-type controls at 7 weeks of age

decreased testis weight ( J:286451 )

• testis weight is significantly reduced at 7 weeks of age

abnormal testis physiology ( J:286451 )

• numbers of 8-OHdG positive cells and gammaH2AX positive cells are dramatically increased in testicular sections, indicating increased DNA damage

decreased testes secretion ( J:286451 )

• testosterone production is reduced and both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice

homeostasis/metabolism

decreased circulating testosterone level ( J:286451 )

• serum testosterone levels are significantly reduced at 7 weeks of age

abnormal enzyme/coenzyme level ( J:286451 )

• both mRNA and protein levels of Hsd3b1 (3betaHSD) and Hsd17b1 (17betaHSD) are significantly downregulated in testis extracts from 7-week-old male mice

• expression levels of antioxidant enzyme genes including Gpx1, Gsr, Cat, Txnrd1 are decreased in testis extracts

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

reproductive system

decreased oocyte number ( J:287217 )

• number of retrieved oocytes per mouse is significantly lower than that for wild-type females

• administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age increases the number of retrieved oocytes significantly but does not restore oocyte number to wild-type levels

decreased mature ovarian follicle number ( J:287217 )

• the number of mature follicles per ovary is markedly reduced at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in mature ovarian follicle number

decreased primary ovarian follicle number ( J:287217 )

• the number of primary follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primary ovarian follicle number

decreased primordial ovarian follicle number ( J:287217 )

• the number of primordial follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primordial ovarian follicle number

decreased secondary ovarian follicle number ( J:287217 )

• the number of secondary follicles per ovary is markedly reduced at 4 and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in secondary ovarian follicle number

increased atretic ovarian follicle number ( J:287217 )

• the number of atretic ovarian follicles is markedly increased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked decrease in atretic follicle number

abnormal ovary development ( J:287217 )

small ovary ( J:287217 )

• ovary size is significantly smaller at 7 weeks of age

• administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age results in a marked increase in ovary size

decreased ovary weight ( J:287217 )

• ovarian weight and ovarian weight/body weight ratio are significantly decreased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in ovarian weight and ovarian weight/body weight ratio

abnormal ovary physiology ( J:287217 )

• protein levels of p16, p19 and p53 are markedly increased whereas anti-apoptotic BCL-2 protein levels are decreased in ovarian extracts from 7-week-old female mice

• numbers of 8-OHdG+ cells and gammaH2AX+ cells are dramatically increased in ovarian sections at 7 weeks of age, indicating increased DNA damage

• % of BrdU+ cells is significantly reduced at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced numbers of 8-OHdG+ cells and gammaH2AX+ cells while % of BrdU+ cells is increased

increased granulosa cell apoptosis ( J:287217 )

• % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

• % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age

delayed vaginal opening ( J:287217 )

• vaginal opening time is markedly delayed

decreased superovulation rate ( J:287217 )

• following induction of superovulation with PMSG and hCG, significantly fewer oocytes are retrieved from the ampulla portion of 3-week old females relative to similarly treated wild-type females

abnormal estrous cycle ( J:287217 )

prolonged diestrus ( J:287217 )

• % of time spent in diestrus per 5 days is significantly increased

short estrus ( J:287217 )

• % of time spent in estrus per 5 days is significantly reduced

prolonged metestrus ( J:287217 )

• % of time spent in metestrus per 5 days is significantly increased

short proestrus ( J:287217 )

• % of time spent in proestrus per 5 days is significantly reduced

female infertility ( J:287217 )

• female mice mated with adult wild-type males of known fertility for 1 month fail to produce offspring, indicating complete female sterility

cellular

decreased oocyte number ( J:287217 )

• number of retrieved oocytes per mouse is significantly lower than that for wild-type females

abnormal mitochondrial morphology ( J:287217 )

• TEM images of granulosa cells and oocytes showed that the mitochondrial outer membrane is indistinct and defective

abnormal mitochondrial crista morphology ( J:287217 )

• some mitochondrial crest blurring or even swelling is observed in the ovaries

decreased mitochondrial number ( J:287217 )

• the number of mitochondria is significantly reduced in the ovaries at 7 weeks of age

increased granulosa cell apoptosis ( J:287217 )

• % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

• % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age

oxidative stress ( J:287217 )

• flow cytometry analysis showed increased reactive oxygen species (ROS) levels in the ovaries at 7 weeks of age

• mRNA expression levels of antioxidant enzyme genes (Sod1, Sod2, Gpx1, Gsr, Cat, and Txnrd1) and the protein levels of SOD1 and SOD2 are significantly decreased in ovarian extracts from 7-week-old female mice

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly decreased ROS levels while protein levels of SOD1 and SOD2 are significantly increased

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:287217 )

decreased superoxide dismutase level ( J:287217 )

• both mRNA and protein levels of Sod1 (superoxide dismutase 1) and Sod2 (superoxide dismutase 2) are significantly decreased in ovarian extracts from 7-week-old female mice

embryo

failure of zygotic cell division ( J:287217 )

• in vitro, oocytes derived from mice treated with IVF fail to develop into 2-cell stage embryos

• surprisingly, antioxidant NAC supplementation rescues the ability of oocytes to develop into early embryos in vitro (including 2-cells, 4-cells, and blastocysts) to nearly wild-type levels

endocrine/exocrine glands

decreased mature ovarian follicle number ( J:287217 )

• the number of mature follicles per ovary is markedly reduced at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in mature ovarian follicle number

decreased primary ovarian follicle number ( J:287217 )

• the number of primary follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primary ovarian follicle number

decreased primordial ovarian follicle number ( J:287217 )

• the number of primordial follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primordial ovarian follicle number

decreased secondary ovarian follicle number ( J:287217 )

• the number of secondary follicles per ovary is markedly reduced at 4 and 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in secondary ovarian follicle number

increased atretic ovarian follicle number ( J:287217 )

• the number of atretic ovarian follicles is markedly increased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked decrease in atretic follicle number

abnormal ovary development ( J:287217 )

small ovary ( J:287217 )

• ovary size is significantly smaller at 7 weeks of age

• administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age results in a marked increase in ovary size

decreased ovary weight ( J:287217 )

• ovarian weight and ovarian weight/body weight ratio are significantly decreased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in ovarian weight and ovarian weight/body weight ratio

abnormal ovary physiology ( J:287217 )

• protein levels of p16, p19 and p53 are markedly increased whereas anti-apoptotic BCL-2 protein levels are decreased in ovarian extracts from 7-week-old female mice

• numbers of 8-OHdG+ cells and gammaH2AX+ cells are dramatically increased in ovarian sections at 7 weeks of age, indicating increased DNA damage

• % of BrdU+ cells is significantly reduced at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced numbers of 8-OHdG+ cells and gammaH2AX+ cells while % of BrdU+ cells is increased

increased granulosa cell apoptosis ( J:287217 )

• % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

• antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

• % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age

Allelic Composition	Bmi1^tm1Brn/Bmi1⁺
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)

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

skeleton

thoracic vertebral transformation ( J:134271 )

• transformation of T13 to L1 is seen in 13% of heterozygous mice

cervical vertebral transformation ( J:134271 )

• partial or complete transformation of C7 to T1 is seen in 31% and 19% of heterozygous mice, respectively

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 50% of heterozygous mice

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn Apc^tm2Cip/Apc⁺ Cdkn2a^tm1Cjs/Cdkn2a^tm1Cjs Tg(Vil1-cre)20Syr/0
Genetic Background	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apc^tm2Cip mutation (0 available); any Apc mutation (158 available)
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)
Cdkn2a^tm1Cjs mutation (7 available); any Cdkn2a mutation (67 available)
Tg(Vil1-cre)20Syr mutation (4 available)

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

growth/size/body

cachexia ( J:204354 )

• found in some animals by 90 days of age

behavior/neurological

hunched posture ( J:204354 )

• hunching appears in some animals at 90 days of age

neoplasm

increased intestinal adenoma incidence ( J:204354 )

• increased size and number of small intestine adenomas

digestive/alimentary system

increased intestinal adenoma incidence ( J:204354 )

• increased size and number of small intestine adenomas

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn Apc^tm2Cip/Apc⁺ Tg(Vil1-cre)20Syr/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * DBA/2

Find Mice

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

neoplasm

decreased alimentary system tumor incidence ( J:204354 )

• tumors in small intestine are almost absent at 120 days of age

• fewer and smaller tumors at 90 days of age as well

• decrease in numbers of tumors between 90 and 120 days

• no increase in tumor size between 90 and 120 days

decreased colon tumor incidence ( J:204354 )

• also reduced at 120 days

decreased intestinal adenoma incidence ( J:204354 )

• adenomas are one tenth the size of those found in controls at 120 days of age

• increased cell proliferation in adenomas at 90 days

• increased apoptosis in smaller adenomas but not larger ones at 90 days

• apoptosis is also increased in non tumor tissue

cellular

increased apoptosis ( J:204354 )

• increased apoptosis in smaller adenomas but not larger ones at 90 days

• apoptosis is also increased in non tumor tissue

digestive/alimentary system

decreased alimentary system tumor incidence ( J:204354 )

• tumors in small intestine are almost absent at 120 days of age

• fewer and smaller tumors at 90 days of age as well

• decrease in numbers of tumors between 90 and 120 days

• no increase in tumor size between 90 and 120 days

decreased colon tumor incidence ( J:204354 )

• also reduced at 120 days

decreased intestinal adenoma incidence ( J:204354 )

• adenomas are one tenth the size of those found in controls at 120 days of age

• increased cell proliferation in adenomas at 90 days

• increased apoptosis in smaller adenomas but not larger ones at 90 days

• apoptosis is also increased in non tumor tissue

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn Rnf2^tm1Mvl/Rnf2⁺
Genetic Background	involves: 129/Ola * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)
Rnf2^tm1Mvl mutation (0 available); any Rnf2 mutation (36 available)

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

mortality/aging

premature death ( J:82399 )

• mutants die at 4-5 weeks of age, earlier than single homozygous Bmi1 mutants

growth/size/body

decreased body size ( J:82399 )

decreased body weight ( J:82399 )

postnatal growth retardation ( J:82399 )

• delay in postnatal development at P10, from which point onward, growth ceases almost entirely

behavior/neurological

impaired coordination ( J:82399 )

• severe lack of coordination

abnormal gait ( J:82399 )

• mutants exhibit a more abnormal gait than single homozygous Bmi1 mutants impaired coordination [MP:0001405

nervous system

abnormal Purkinje cell dendrite morphology ( J:82399 )

• arborization of Purkinje cells in the molecular layer is different, with thicker and less branched dendrites

abnormal cerebellar granule layer morphology ( J:82399 )

• reduction in cellularity and size of the granular layer of the cerebellum

abnormal cerebellar molecular layer ( J:82399 )

• reduction in cellularity and size of the molecular layer of the cerebellum

small cerebellum ( J:82399 )

gliosis ( J:82399 )

skeleton

abnormal axial skeleton morphology ( J:82399 )

• mutants exhibit axial skeleton abnormalities in the cervical, thoracic, lumbar and sacral regions

Allelic Composition	Pcgf2^tm1Hko/Pcgf2^tm1Hko Bmi1^tm1Brn/Bmi1⁺
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)
Pcgf2^tm1Hko mutation (2 available); any Pcgf2 mutation (48 available)

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

craniofacial

abnormal craniofacial bone morphology ( J:68216 )

split exoccipital bone ( J:68216 )

cleft secondary palate ( J:68216 )

skeleton

abnormal scapula morphology ( J:68216 )

acromion hypoplasia ( J:68216 )

• acromion is poorly formed

scapular bone foramen ( J:68216 )

• holes are seen in the blade of the scapula

abnormal axial skeleton morphology ( J:68216 )

abnormal craniofacial bone morphology ( J:68216 )

split exoccipital bone ( J:68216 )

abnormal rib joint morphology ( J:68216 )

• rudimentary ribs attached to C6

abnormal cervical atlas morphology ( J:68216 )

• atlas resembles the third cervical vertebra

cervical vertebral transformation ( J:68216 )

• atlas resembles the third cervical vertebra

abnormal sternum ossification ( J:68216 )

• ectopic ossification centers in sternum

digestive/alimentary system

cleft secondary palate ( J:68216 )

growth/size/body

cleft secondary palate ( J:68216 )

Allelic Composition	Pcgf2^tm1Hko/Pcgf2⁺ Bmi1^tm1Brn/Bmi1^tm1Brn
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

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

craniofacial

abnormal craniofacial bone morphology ( J:68216 )

split exoccipital bone ( J:68216 )

cleft secondary palate ( J:68216 )

skeleton

abnormal scapula morphology ( J:68216 )

acromion hypoplasia ( J:68216 )

• acromion is poorly formed

scapular bone foramen ( J:68216 )

• holes are seen in the blade of the scapula

abnormal axial skeleton morphology ( J:68216 )

abnormal craniofacial bone morphology ( J:68216 )

split exoccipital bone ( J:68216 )

abnormal rib joint morphology ( J:68216 )

• rudimentary ribs attached to C6

abnormal cervical atlas morphology ( J:68216 )

• atlas resembles the third cervical vertebra

cervical vertebral transformation ( J:68216 )

• atlas resembles the third cervical vertebra

abnormal sternum ossification ( J:68216 )

• ectopic ossification centers in sternum

digestive/alimentary system

cleft secondary palate ( J:68216 )

growth/size/body

cleft secondary palate ( J:68216 )

Allelic Composition	Pcgf2^tm1Hko/Pcgf2^tm1Hko Bmi1^tm1Brn/Bmi1^tm1Brn
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:68216 )

• double homozygotes die around E9.5

cardiovascular system

abnormal dorsal aorta morphology ( J:68216 )

• dorsal aorta is expanded in the caudal region

embryo

abnormal first pharyngeal arch morphology ( J:68216 )

• first branchial arches were poorly developed

abnormal second pharyngeal arch morphology ( J:68216 )

• second branchial arches were poorly developed

embryonic growth arrest ( J:68216 )

• development was normal at E8.5 but mice were severely growth retarded at E9.5

abnormal somatic mesoderm morphology ( J:68216 )

• somatic mesoderm was appropriately segmented but irregularly aligned

abnormal neural tube morphology ( J:68216 )

• neural tube is small

• cell to cell adhesion is impaired in the neural tube

abnormal notochord morphology ( J:68216 )

• fusion with hindgut endoderm seen

small notochord ( J:68216 )

• reduced

split notochord ( J:68216 )

• bifurcated

abnormal somite development ( J:68216 )

• 18 as opposed to the normal 24 somites at E9.5

abnormal tail bud morphology ( J:68216 )

• distal tip of the tail bud is shrunken

nervous system

increased neural tube apoptosis ( J:68216 )

• apoptosis is seen in the neural tube

abnormal neural tube morphology ( J:68216 )

• neural tube is small

• cell to cell adhesion is impaired in the neural tube

abnormal brain morphology ( J:68216 )

hindbrain hypoplasia ( J:68216 )

• hindbrain is underdeveloped

skeleton

abnormal cervical atlas morphology ( J:68216 )

• atlas resembles the third cervical vertebra

cervical vertebral transformation ( J:68216 )

• atlas resembles the third cervical vertebra

craniofacial

abnormal first pharyngeal arch morphology ( J:68216 )

• first branchial arches were poorly developed

abnormal second pharyngeal arch morphology ( J:68216 )

• second branchial arches were poorly developed

limbs/digits/tail

abnormal tail bud morphology ( J:68216 )

• distal tip of the tail bud is shrunken

vision/eye

abnormal optic eminence morphology ( J:68216 )

• optic eminence was obscure

cellular

increased neural tube apoptosis ( J:68216 )

• apoptosis is seen in the neural tube

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn E2f6^tm1Lees/E2f6⁺
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bmi1^tm1Brn mutation (2 available); any Bmi1 mutation (31 available)
E2f6^tm1Lees mutation (0 available); any E2f6 mutation (15 available)

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

skeleton

abnormal vertebrae morphology ( J:134271 )

• small extra bone present above C1 in 62% of compound mutant mice

thoracic vertebral transformation ( J:134271 )

• transformation of T7 to T8 and T13 to L1 are seen in 77% and 85% of compound mutant mice, respectively

cervical vertebral transformation ( J:134271 )

• transformation of C1 to C2, C5 to C6, and C7 to T1 are seen in 85%, 23%, and 31% of compound mutant mice, respectively

• partial transformation of C7 to T1 is seen in 77% of compound mutant mice

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 92% of compound mutant mice

Allelic Composition	Bmi1^tm1Brn/Bmi1^tm1Brn E2f6^tm1Lees/E2f6^tm1Lees
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Find Mice

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

mortality/aging

premature death ( J:134271 )

• lethality is seen between 3 and 20 weeks of age

postnatal lethality, incomplete penetrance ( J:134271 )

• only 38% of the expected number of mice are present at weaning

prenatal lethality, incomplete penetrance ( J:134271 )

• only 46% of the expected number of embryos are present at E18.5

growth/size/body

postnatal growth retardation ( J:134271 )

skeleton

abnormal vertebrae morphology ( J:134271 )

• small extra bone present above C1 in 38% of double homozygous mice

thoracic vertebral transformation ( J:134271 )

• transformation of T7 to T8 and T13 to L1 are seen in 62% and 100% of double homozygous mice, respectively

cervical vertebral transformation ( J:134271 )

• transformation of C1 to C2, C5 to C6, and C7 to T1 are seen in 92%, 23%, and 8% of double homozygous mice, respectively

• partial transformation of C7 to T1 is seen in 85% of double homozygous mice

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 100% of double homozygous mice

hematopoietic system

anemia ( J:134271 )

• severe

abnormal bone marrow cell morphology/development ( J:134271 )

• shift in the distribution of myeloid to B lymphoid cells resulting in an increased percentage of myeloid cells

• within the B cell population, loss of immature B cells is greater than the loss of mature B cells

decreased bone marrow cell number ( J:134271 )

decreased hematopoietic cell number ( J:134271 )

• decreased number of hematopoietic cells in the thymus, bone marrow and spleen

decreased double-positive T cell number ( J:134271 )

cellular

abnormal cell cycle ( J:134271 )

• impaired ability of serum-starved MEFs to re-enter the cell cycle

decreased cell proliferation ( J:134271 )

• defect in asynchronous proliferation in MEFs

early cellular replicative senescence ( J:134271 )

• in MEFs

behavior/neurological

ataxia ( J:134271 )

• similar to that seen in mice homozygous for Bmi1^tm1Brn alone at 2 months of age

nervous system

cerebellum hypoplasia ( J:134271 )

• all three layers are affected

• hypoplasia is similar to that in mice homozygous for Bmi1^tm1Brn alone

immune system

decreased double-positive T cell number ( J:134271 )

Allelic Composition	Bmi1^tm1Brn/Bmi1⁺ E2f6^tm1Lees/E2f6^tm1Lees
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Find Mice

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

skeleton

thoracic vertebral transformation ( J:134271 )

• transformation of T13 to L1 is seen in 77% of compound mutant mice

cervical vertebral transformation ( J:134271 )

• partial or complete transformation of C7 to T1 is seen in 27% and 4% of compound mutant mice, respectively

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 92% of compound mutant mice

Allelic Composition	Bmi1^tm1Brn/Bmi1⁺ E2f6^tm1Lees/E2f6⁺
Genetic Background	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Find Mice

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

skeleton

thoracic vertebral transformation ( J:134271 )

• transformation of T7 to T8 and T13 to L1 are seen in 4% and 50% of double heterozygous mice, respectively

cervical vertebral transformation ( J:134271 )

• partial or complete transformation of C7 to T1 is seen in 42% and 8% of double heterozygous mice, respectively

• transformation of C5 to C6 is seen in 4% of double heterozygous mice

lumbar vertebral transformation ( J:134271 )

• transformation of L6 to S1 is seen in 73% of double heterozygous mice

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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