Phenotypes associated with this allele

• Allele Symbol: Trp53bp2^tm1Xlu
• Allele Name: targeted mutation 1, Xin Lu
• Allele ID: MGI:3625686
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu	B6.129S6-Trp53bp2^tm1Xlu	MGI:6191758
hm2	Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu	C.129S6-Trp53bp2^tm1Xlu	MGI:4819168
hm3	Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu	involves: 129S6/SvEvTac * C57BL/6J	MGI:3629203
ht4	Trp53bp2^tm1Xlu/Trp53bp2^+	B6.129S6-Trp53bp2^tm1Xlu	MGI:6191759
ht5	Trp53bp2^tm1Xlu/Trp53bp2^+	C.129S6-Trp53bp2^tm1Xlu	MGI:6191760
ht6	Trp53bp2^tm1Xlu/Trp53bp2^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:3629204
cx7	Trp53^tm1Tyj/Trp53^+ Trp53bp2^tm1Xlu/Trp53bp2^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:3629207
cx8	Trp53^tm1Tyj/Trp53^+ Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:3629206
cx9	Trp53^tm1Tyj/Trp53^tm1Tyj Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J	MGI:3629205

Genotype
MGI:6191758

hm1

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu
• Genetic Background: B6.129S6-Trp53bp2^tm1Xlu

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

mortality/aging

neonatal lethality, complete penetrance ( J:240594 )

• 100% neonatal lethality, with no mice surviving after birth

growth/size/body

micrognathia ( J:240594 )

• in some embryos

cleft palate ( J:240594 )

• 67% of embryos have cleft palate

narrow head ( J:240594 )

• dolichocephaly in some embryos

cardiovascular system

umbilical vein stenosis ( J:240594 )

• narrow umbilical vein in 50% of embryos

ductus venosus stenosis ( J:240594 )

• narrow ductus venosus in 50% of mice

abnormal heart position or orientation ( J:240594 )

• embryos have abnormal heart position involving a 30-40 degree twist along the coronal axis at E13.5 and E14.5

ventricular septal defect ( J:240594 )

• 67% of embryos have a ventricular septal defect

intracranial hemorrhage ( J:240594 )

• 31% of embryos exhibit intracranial hemorrhages

craniofacial

micrognathia ( J:240594 )

• in some embryos

cleft palate ( J:240594 )

• 67% of embryos have cleft palate

narrow head ( J:240594 )

• dolichocephaly in some embryos

digestive/alimentary system

cleft palate ( J:240594 )

• 67% of embryos have cleft palate

embryo

umbilical vein stenosis ( J:240594 )

• narrow umbilical vein in 50% of embryos

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 46% of embryos exhibit neural tube defects, a much higher percentage than on the BALB/c or mixed backgrounds

• neural tube defects range from spina bifida to craniorachischisis with some spina bifida

• occasional overgrowth of neural tissue is seen in embryos with neural tube defects

spina bifida ( J:240594 )

• seen in some embryos

craniorachischisis ( J:240594 )

• seen in some embryos

wavy neural tube ( J:240594 )

• spinal column of the neural tube is often wrinkled, even in embryos without neural tube defects

endocrine/exocrine glands

abnormal sex gland morphology ( J:240594 )

• a high percentage of embryos exhibit gonadal abnormalities resulting in unclear sex at E14.5

nervous system

intracranial hemorrhage ( J:240594 )

• 31% of embryos exhibit intracranial hemorrhages

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 46% of embryos exhibit neural tube defects, a much higher percentage than on the BALB/c or mixed backgrounds

• neural tube defects range from spina bifida to craniorachischisis with some spina bifida

• occasional overgrowth of neural tissue is seen in embryos with neural tube defects

spina bifida ( J:240594 )

• seen in some embryos

craniorachischisis ( J:240594 )

• seen in some embryos

wavy neural tube ( J:240594 )

• spinal column of the neural tube is often wrinkled, even in embryos without neural tube defects

abnormal trigeminal nerve morphology ( J:240594 )

• a high percentage of embryos exhibit abnormal trigeminal nerve

abnormal dorsal root ganglion morphology ( J:240594 )

• a high percentage of embryos exhibit abnormal spinal ganglia

renal/urinary system

abnormal urethra morphology ( J:240594 )

• a high percentage of embryos exhibit urethral abnormalities

reproductive system

abnormal sex gland morphology ( J:240594 )

• a high percentage of embryos exhibit gonadal abnormalities resulting in unclear sex at E14.5

skeleton

micrognathia ( J:240594 )

• in some embryos

vision/eye

coloboma ( J:240594 )

• seen in some embryos

microphthalmia ( J:240594 )

• seen in some embryos

abnormal retina morphology ( J:240594 )

• retinal abnormalities

anophthalmia ( J:240594 )

• some mice show uni/bi-lateral eye agenesis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chromosome 1q41-q42 deletion syndrome		DOID:0060412	OMIM:612530	J:240594

Genotype
MGI:4819168

hm2

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu
• Genetic Background: C.129S6-Trp53bp2^tm1Xlu

mortality/aging

mortality/aging ( J:162396 )

N • Background Sensitivity: unlike mice on a mixed 129/Sv and C57BL/6J background, the majority of mice survive past weaning

behavior/neurological

abnormal gait ( J:240594 )

• surviving mice have a 100% incidence of hop gait

nervous system

intracranial hemorrhage ( J:240594 )

• 50% of embryos exhibit intracranial hemorrhages

intraventricular hemorrhage ( J:240594 )

• 50% of embryos exhibit subcranial and intraventricular hemorrhages

abnormal neuron differentiation ( J:162396 )

• overall reduction in the number of differentiated neurons in the cortex at E14.5

abnormal neuronal migration ( J:162396 )

• at E14.5 mitotic cells are found scattered up the cortical plate rather than being mostly confined to the ventricular surface as in controls

• interkinetic nuclear migration within the ventricular zone is disturbed with a reduction in the percentage of BrdU positive cells on the apical side of the zone

• betaIII tubulin expressing post mitotic neurons are found in the ventricular zone suggesting a defect in radial migration

• late born neurons are mislocalized in the cortex at P15

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 8% of embryos exhibit a neural tube defect, a much smaller percentage than on the C57BL/6 background

abnormal embryonic neuroepithelium morphology ( J:162396 )

• at E13.5 the cytoarchitecture of the neuroepithelium is disorganized and polarity of progenitor cells is lost in the ganglionic eminence

abnormal brain morphology ( J:162396 )

• extensive morphological abnormalities are detected at E13.5

abnormal pineal gland morphology ( J:240594 )

• the pineal gland is absent or severely hypoplastic in nearly all embryos

absent pineal gland ( J:240594 )

abnormal cortical plate morphology ( J:162396 )

• at E14.5 mitotic cells are found scattered up the cortical plate

abnormal cortical ventricular zone morphology ( J:162396 )

• betaIII tubulin expressing post mitotic neurons are found in the ventricular zone

hydrocephaly ( J:162396 )

• in all mice

enlarged brain ventricles ( J:240594 )

• brain ventricles are enlarged in about 50% of embryos at E13.5 and E14.5

abnormal lateral ventricle morphology ( J:240594 )

• bodies of the lateral ventricles are more parallel and bulbous than in controls

abnormal choroid plexus morphology ( J:162396 )

• in mice with very mild hydroencephaly epithelial cells are rounded, the epithelium is disorganized and the tight/adherens junctions between cells are less electron-dense

• many of the tight/adherens junctions at the apical poles of choroid plexus cells fail to form tightly closed electron-dense junctions

abnormal cerebral cortex morphology ( J:162396 )

• overall reduction in the number of differentiated neurons in the cortex at E14.5

• late born neurons are mislocalized in the cortex at P15

abnormal stratification in cerebral cortex ( J:162396 )

• cells expressing SMI32 (a marker of layers III and V) are mislocalized at P15

abnormal olfactory bulb morphology ( J:240594 )

• olfactory bulbs are not pronounced well in 67% of embryos

abnormal embryonic/fetal subventricular zone morphology ( J:162396 )

• the cytoarchitecture of the neuroepithelium is disorganized and polarity of progenitor cells is lost

exencephaly ( J:240594 )

• exencephaly is the only neural tube defect seen

absent abducens nerve ( J:240594 )

• 33% of embryos lack the abducens nerve

abnormal spinal cord central canal morphology ( J:240594 )

• spinal canal is abnormal in all embryos, with abnormal stenosis, presence of blood, or small cyst-like structures in the caudal part of the neural tube

• all embryos have abnormalities in the cerebrospinal fluid space with blockage and/or hemorrhage in at least one part of the ventricular system and/or spinal canal

abnormal embryonic neuroepithelial cell proliferation ( J:162396 )

• at E13.5 abnormal growth of neuroepithelial cells is seen at the level of the third ventricle and in the ganglionic eminence the cytoarchitecture of the neuroepithelium is disorganized and polarity of progenitor cells is lost

• Background Sensitivity: the extent of abnormal cell growth is less dramatic in mice on an inbred BALB/c background compared to mice on a mixed 129/Sv and C57BL/6J background

cardiovascular system

ductus venosus stenosis ( J:240594 )

• narrow ductus venosus in 67% of mice

abnormal heart position or orientation ( J:240594 )

• embryos have abnormal heart position involving a 30-40 degree twist along the coronal axis at E13.5 and E14.5

ventricular septal defect ( J:240594 )

• 33% of embryos have a ventricular septal defect

intracranial hemorrhage ( J:240594 )

• 50% of embryos exhibit intracranial hemorrhages

intraventricular hemorrhage ( J:240594 )

• 50% of embryos exhibit subcranial and intraventricular hemorrhages

vision/eye

abnormal retina morphology ( J:162396 , J:240594 )

• retinal dysplasia is seen in all mice, similar to that seen in mice on a mixed 129/Sv and C57BL/6J background (J:162396)

• extensive morphological abnormalities are detected at E13.5 (J:162396)

• retinal abnormalities (J:240594)

disorganized retina layers ( J:162396 )

• severe disruption of lamination at P15 with mislocalization of rods, cones, Muller glia, horizontal cells, amacrine cells, and retinal ganglionic cells

craniofacial

cleft palate ( J:240594 )

• 33% of embryos have cleft palate

cellular

abnormal neuron differentiation ( J:162396 )

• overall reduction in the number of differentiated neurons in the cortex at E14.5

abnormal neuronal migration ( J:162396 )

• at E14.5 mitotic cells are found scattered up the cortical plate rather than being mostly confined to the ventricular surface as in controls

• interkinetic nuclear migration within the ventricular zone is disturbed with a reduction in the percentage of BrdU positive cells on the apical side of the zone

• betaIII tubulin expressing post mitotic neurons are found in the ventricular zone suggesting a defect in radial migration

• late born neurons are mislocalized in the cortex at P15

digestive/alimentary system

cleft palate ( J:240594 )

• 33% of embryos have cleft palate

endocrine/exocrine glands

abnormal pineal gland morphology ( J:240594 )

• the pineal gland is absent or severely hypoplastic in nearly all embryos

absent pineal gland ( J:240594 )

small thymus ( J:240594 )

• in 67% of mice

embryo

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 8% of embryos exhibit a neural tube defect, a much smaller percentage than on the C57BL/6 background

abnormal embryonic neuroepithelium morphology ( J:162396 )

• at E13.5 the cytoarchitecture of the neuroepithelium is disorganized and polarity of progenitor cells is lost in the ganglionic eminence

growth/size/body

cleft palate ( J:240594 )

• 33% of embryos have cleft palate

hematopoietic system

small thymus ( J:240594 )

• in 67% of mice

immune system

small thymus ( J:240594 )

• in 67% of mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chromosome 1q41-q42 deletion syndrome		DOID:0060412	OMIM:612530	J:240594

Genotype
MGI:3629203

hm3

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

mortality/aging

postnatal lethality, complete penetrance ( J:108701 , J:162396 )

• majority of homozygotes die between 6 and 30 days postnatal; remainder die shortly after weaning; postnatal death due to combination of hydrocephalus and heart defects (data not shown) (J:108701)

• Background Sensitivity: unlike mice on an inbred BALB/c background all mice die before weaning (J:162396)

perinatal lethality, incomplete penetrance ( J:108701 , J:162396 )

• expected numbers of homozygotes survived to E18.5, but homozygous pups found after birth is far below expected frequency (data not shown) (J:108701)

• about 30% of homozygous pups survive to birth (J:162396)

digestive/alimentary system

cleft palate ( J:240594 )

• in some embryos

embryo

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 15% of embryos have neural tube defects, an intermediate percentage on the mixed background compared to on a C57BL/6 or BALB/c background

• neural tube defects are small at early stages (E9.5-E10.5) and progress to larger lesions after E13.5

• neural tube defects mainly are exencephaly and rostral spinal bifida and rarely craniorachischisis

spina bifida ( J:240594 )

craniorachischisis ( J:240594 )

• seen only rarely

growth/size/body

micrognathia ( J:240594 )

• in some embryos

cleft palate ( J:240594 )

• in some embryos

narrow head ( J:240594 )

• dolichocephaly in some embryos

decreased body size ( J:108701 , J:162396 )

• homozygotes surviving birth are runted (J:108701)

• surviving pups are about 1.5 - 2 times smaller than littermate controls (J:162396)

craniofacial

micrognathia ( J:240594 )

• in some embryos

domed cranium ( J:108701 )

• homozygotes surviving birth have a domed head shape

cleft palate ( J:240594 )

• in some embryos

narrow head ( J:240594 )

• dolichocephaly in some embryos

endocrine/exocrine glands

abnormal sex gland morphology ( J:240594 )

• a high percentage of embryos exhibit gonadal abnormalities resulting in unclear sex at E14.5

renal/urinary system

abnormal urethra morphology ( J:240594 )

• a high percentage of embryos exhibit urethral abnormalities

nervous system

increased neuron apoptosis ( J:162396 )

• increase in the number of apoptotic cells in the brain at E13.5

abnormal neuronal precursor proliferation ( J:162396 )

• about a 2 to 2.5 fold increase in the mitotic index in the neural tube at E11.5 and E13.5

• increase in the percentage of BrdU positive cells in the ganglionic eminence suggesting a shortening of the cell cycle of neural progenitors

abnormal neural tube morphology ( J:240594 )

• Background Sensitivity: 15% of embryos have neural tube defects, an intermediate percentage on the mixed background compared to on a C57BL/6 or BALB/c background

• neural tube defects are small at early stages (E9.5-E10.5) and progress to larger lesions after E13.5

• neural tube defects mainly are exencephaly and rostral spinal bifida and rarely craniorachischisis

spina bifida ( J:240594 )

craniorachischisis ( J:240594 )

• seen only rarely

abnormal brain morphology ( J:162396 )

• extensive morphological abnormalities are detected at E13.5

abnormal cortical ventricular zone morphology ( J:162396 )

• at E13.5 cells in the VZ are disorganized, less columnar, and protrude into the ventricles

hydrocephaly ( J:162396 )

• in all pups at P5 - P30

dilated brain ventricle ( J:162396 )

• drastically dilated with severe damage to the subventricular structures

abnormal embryonic/fetal subventricular zone morphology ( J:162396 )

• at E13.5 the normal radial orientation of progenitor cells in the ganglionic eminence is lost

exencephaly ( J:240594 )

increased neuronal precursor cell number ( J:162396 )

abnormal trigeminal nerve morphology ( J:240594 )

• a high percentage of embryos exhibit abnormal trigeminal nerve

abnormal dorsal root ganglion morphology ( J:240594 )

• a high percentage of embryos exhibit abnormal spinal ganglia

abnormal embryonic neuroepithelial cell proliferation ( J:162396 )

• at E13.5 abnormal growth of neuroepithelial cells is seen either at the level of the third ventricle or throughout the brain

• at E13.5 rosettes are seen in the neuroepithelium and highly proliferative neural progenitors are spread throughout the proliferating neuroepithelium rather than being confined to the ventricular zone of the telencephalon as in controls

• Background Sensitivity: the extent of abnormal cell growth is more dramatic in mice on a mixed 129/Sv and C57BL/6J background compared to mice on an inbred BALB/c background

• severe over-expansion frequently prevents the identification of forebrain structures

increased embryonic neuroepithelial cell proliferation ( J:162396 )

• about a 2 to 2.5 fold increase in the mitotic index at E11.5 and E13.5

vision/eye

abnormal retina morphology ( J:162396 )

• most common retinal defect is bilateral retinal dysplasia

• extensive morphological abnormalities are detected at E13.5

abnormal retina progenitor cell morphology ( J:162396 )

• at E13.5 progenitor cells in the central region are arranged in rosette-like structures

abnormal retina outer nuclear layer morphology ( J:162396 )

• dysplastic rosettes are present in mice with bilateral retinal dysplasia

abnormal retina photoreceptor layer morphology ( J:162396 )

• dysplastic rosettes are present in mice with bilateral retinal dysplasia

reproductive system

abnormal sex gland morphology ( J:240594 )

• a high percentage of embryos exhibit gonadal abnormalities resulting in unclear sex at E14.5

skeleton

micrognathia ( J:240594 )

• in some embryos

domed cranium ( J:108701 )

• homozygotes surviving birth have a domed head shape

cellular

increased neuron apoptosis ( J:162396 )

• increase in the number of apoptotic cells in the brain at E13.5

abnormal neuronal precursor proliferation ( J:162396 )

• about a 2 to 2.5 fold increase in the mitotic index in the neural tube at E11.5 and E13.5

• increase in the percentage of BrdU positive cells in the ganglionic eminence suggesting a shortening of the cell cycle of neural progenitors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
chromosome 1q41-q42 deletion syndrome		DOID:0060412	OMIM:612530	J:240594

Genotype
MGI:6191759

ht4

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2⁺
• Genetic Background: B6.129S6-Trp53bp2^tm1Xlu

cardiovascular system

ventricular septal defect ( J:240594 )

• 30% incidence of ventricular septal defect

craniofacial

cleft palate ( J:240594 )

• 30% incidence of cleft palate

digestive/alimentary system

cleft palate ( J:240594 )

• 30% incidence of cleft palate

growth/size/body

cleft palate ( J:240594 )

• 30% incidence of cleft palate

nervous system

abnormal spinal cord central canal morphology ( J:240594 )

• 20% incidence of spinal canal abnormalities

vision/eye

abnormal retina morphology ( J:240594 )

• 30% incidence of retinal abnormalities

Genotype
MGI:6191760

ht5

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2⁺
• Genetic Background: C.129S6-Trp53bp2^tm1Xlu

cardiovascular system

ventricular septal defect ( J:240594 )

• 13% incidence of ventricular septal defect

hemorrhage ( J:240594 )

• small patches of subcranial hemorrhage

embryo

abnormal embryonic neuroepithelium morphology ( J:240594 )

• 25% of embryos show localized abnormalities in the distribution of neuroepithelial brain tissue associated with small patches of subcranial hemorrhage

nervous system

abnormal embryonic neuroepithelium morphology ( J:240594 )

• 25% of embryos show localized abnormalities in the distribution of neuroepithelial brain tissue associated with small patches of subcranial hemorrhage

abnormal lateral ventricle morphology ( J:240594 )

• 25% incidence of asymmetric lateral ventricles

Genotype
MGI:3629204

ht6

• Allelic Composition: Trp53bp2^tm1Xlu/Trp53bp2⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

neoplasm

increased tumor incidence ( J:108701 )

• incidence of tumors (12/20) is much higher in heterozygous mice than in wild-type mice (4/18) over a 3 year period

increased rhabdomyosarcoma incidence ( J:108701 )

• 1/20 spontaneously developed this sarcoma: only observed in irradiated heterozygous mice, not in wild-type

increased lymphoma incidence ( J:108701 )

• 40% of mice develop lymphomas; in wild-type this is the only type of tumor occurring tumor origin is determined to be T and B cell-derived

increased T cell derived lymphoma incidence ( J:108701 )

• T cell lymphomas in various tissues are observed in both irradiated heterozygous and wild-type mice

increased squamous cell carcinoma incidence ( J:108701 )

• 1/20 showed squamous cell carcinoma

increased hemangiosarcoma incidence ( J:108701 )

• 2/20 heterozygotes developed angiosarcoma

increased incidence of tumors by ionizing radiation induction ( J:108701 )

• more irradiated heterozygotes (9/19) develop tumors than untreated heterozygotes (1/19) or irradiated wild-type mice (3/19)

muscle

increased rhabdomyosarcoma incidence ( J:108701 )

• 1/20 spontaneously developed this sarcoma: only observed in irradiated heterozygous mice, not in wild-type

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:108701 )

• T cell lymphomas in various tissues are observed in both irradiated heterozygous and wild-type mice

hematopoietic system

increased T cell derived lymphoma incidence ( J:108701 )

• T cell lymphomas in various tissues are observed in both irradiated heterozygous and wild-type mice

immune system

increased T cell derived lymphoma incidence ( J:108701 )

• T cell lymphomas in various tissues are observed in both irradiated heterozygous and wild-type mice

Genotype
MGI:3629207

cx7

• Allelic Composition: Trp53^tm1Tyj/Trp53⁺; Trp53bp2^tm1Xlu/Trp53bp2⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

neoplasm

increased tumor incidence ( J:108701 )

• 26% of double heterozygotes develop tumors over a 72 week period

increased lymphoma incidence ( J:108701 )

• lymphoma development is accelerated in compared to Trp53 heterozygotes with wild-type Trp53bp2; at 42 weeks there is a significant difference in the onset between the two genotypes

• at 72 weeks the difference in onset of lymphoma development is not significant

Genotype
MGI:3629206

cx8

• Allelic Composition: Trp53^tm1Tyj/Trp53⁺; Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

mortality/aging

prenatal lethality, incomplete penetrance ( J:108701 )

• only 20% of the expected number of pups are found at birth

Genotype
MGI:3629205

cx9

• Allelic Composition: Trp53^tm1Tyj/Trp53^tm1Tyj; Trp53bp2^tm1Xlu/Trp53bp2^tm1Xlu
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6J

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:108701 )

• no homozygous offspring are found in timed matings from E11.5-17.5