Phenotypes associated with this allele

• Allele Symbol: Tg(En2-cre)22Alj
• Allele Name: transgene insertion 22, Alexandra L Joyner
• Allele ID: MGI:2450322
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Jun^tm4Wag/Jun^tm4Wag Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd	MGI:5293752
cn2	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Jun^tm2.1Wag/Jun^tm4Wag Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5293753
cn3	Rb1^tm2Brn/Rb1^tm2Brn Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707497
cn4	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^tm1Htr Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707498
cn5	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^+ Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707499
cn6	Rb1^tm2Brn/Rb1^tm2Brn Rbl1^tm1Htr/Rbl1^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(En2-cre)22Alj/0	involves: 129P2/OlaHsd * CD-1	MGI:3707502
cn7	Pten^tm1Mro/Pten^tm1Mro Tg(En2-cre)22Alj/0	Not Specified	MGI:3805876
cn8	Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj/0	Not Specified	MGI:5293751

Genotype
MGI:5293752

cn1

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Jun^tm4Wag/Jun^tm4Wag; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd

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

nervous system

abnormal Purkinje cell morphology ( J:176598 )

• Purkinje cells exhibit partial rescue of organization and arborization compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

• however, Purkinje cell density is rescued

abnormal cerebellum fissure morphology ( J:176598 )

• supranumeral fissures

small cerebellum ( J:176598 )

• partially rescued compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

Genotype
MGI:5293753

cn2

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Jun^tm2.1Wag/Jun^tm4Wag; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

nervous system

abnormal Purkinje cell morphology ( J:176598 )

• Purkinje cells exhibit partial rescue of organization and arborization compared with Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe Tg(En2-cre)22Alj mice

• however, Purkinje cell density is rescued

small cerebellum ( J:176598 )

Genotype
MGI:3707497

cn3

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

nervous system

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30 and is accelerated compared to Rb1 single mutant mice

• there is no detectable Purkinje cell apoptosis

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in cerebellum is higher than in controls; at P20, proliferation in external granule layer (EGL) of vermis is increased while in the internal granule layer (IGL), higher proliferation is detected at P8

abnormal cerebellum external granule cell layer morphology ( J:83783 )

• at P 15, thickness of the external granule layer (EGL) is greater (4-5 cells thick) relative to wild-type (1 or 2 cells thick)

thin external granule cell layer ( J:83783 )

• at P20, mice have a persisten thin EGL with granule cell precursors still migrating through the molecular layer

abnormal brain interneuron morphology ( J:83783 )

• interneurons of molecular layer of cerebellum are substantially reduced in number at P20, which is most pronounced in lobules VI and VII

abnormal cerebellar cortex morphology ( J:83783 )

• numbers of granule, basket and stellate neurons are considerably reduced compared to wild-type

abnormal Purkinje cell morphology ( J:83783 )

• Purkinje cells are slightly irregularly arranged and have moderately enlarged somata and nuclei

• Purkinje cells in vermis appear disarranged, and occasionally show enlarged nuclei with abnormal shapes and reduced dendritic arborization

abnormal cerebellar granule layer morphology ( J:83783 )

• thickness and cellularity of the internal granule layer (IGL ) is reduced at P20 compared to wild-type; this is most pronounced in lobules VI and VII

abnormal cerebellar granule cell morphology ( J:83783 )

• numbers are severely reduced in cerebellum

astrocytosis ( J:83783 )

• a brisk widespread astrogliosis in observed in the IGL

cellular

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30 and is accelerated compared to Rb1 single mutant mice

• there is no detectable Purkinje cell apoptosis

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in cerebellum is higher than in controls; at P20, proliferation in external granule layer (EGL) of vermis is increased while in the internal granule layer (IGL), higher proliferation is detected at P8

Genotype
MGI:3707498

cn4

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1^tm1Htr; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

behavior/neurological

ataxia ( J:83783 )

• mutants develop ataxia between P15 and P20

nervous system

abnormal neuronal precursor proliferation ( J:83783 )

• increased proliferation is even more pronounced in cerebella of mutants at P15 and 20

abnormal cerebellar cortex morphology ( J:83783 )

• at P20, mice have highly disorganized cerebellar architecture in median cerebellar region

abnormal Purkinje cell morphology ( J:83783 )

• dendritic arborization appears shrunken, with stunted to misoriented dendrites

• cell bodies are poorly aligned with loss of laminar distribution

• occasionally bi-nucleated neurons are observed

thin cerebellar molecular layer ( J:83783 )

• layer is reduce in size

abnormal cerebellum vermis morphology ( J:83783 )

• at P15, the vermis is severely reduced in size

cellular

abnormal neuronal precursor proliferation ( J:83783 )

• increased proliferation is even more pronounced in cerebella of mutants at P15 and 20

Genotype
MGI:3707499

cn5

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1⁺; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

behavior/neurological

ataxia ( J:83783 )

• mutants develop ataxia between P15 and P20

nervous system

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in external granule layer is higher than in controls

abnormal cerebellum vermis morphology ( J:83783 )

• at P15, the vermis is considerably reduced in size, but less than when both Rbl1 alleles are lost

cerebellum hypoplasia ( J:83783 )

• at P15, size reduction compared to wild-type cerebella is noticed

cellular

increased neuron apoptosis ( J:83783 )

• increase in apoptotic rate is seen at P15 in vermis of mutants; most apoptotic cells are found in the inner half of the external granule layer and in the inner granule layer; rate is similar at P30

abnormal neuronal precursor proliferation ( J:83783 )

• at P15, number of proliferating granule cell precursors in external granule layer is higher than in controls

Genotype
MGI:3707502

cn6

• Allelic Composition: Rb1^tm2Brn/Rb1^tm2Brn; Rbl1^tm1Htr/Rbl1⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(En2-cre)22Alj/0
• Genetic Background: involves: 129P2/OlaHsd * CD-1

cellular

cellular phenotype ( J:83783 )

N • mice have similar levels of apoptosis in the cerebella as Rb1, Rbl1 double mutants which express Trp53

Genotype
MGI:3805876

cn7

• Allelic Composition: Pten^tm1Mro/Pten^tm1Mro; Tg(En2-cre)22Alj/0
• Genetic Background: Not Specified

nervous system

abnormal neuronal migration ( J:77123 )

• migration of Purkinje cells is impaired with the majority of cells clustering above the fourth ventricle without recognizable orientation

• Golgi, stellate, basket, Bergmann glial and oligodendrocyte cells fail to migrate properly and are randomly distributed throughout the cerebellum

abnormal cerebellum morphology ( J:77123 )

• at P1 and P9, cerebellar cell proliferation is increased and cell death is decreased compared to in wild-type mice

abnormal cerebellum development ( J:77123 )

• at E15.5, mice exhibit increased precursor cell size resulting in an increase in cerebellar anlage size

• at E15.5, cerebellar cell proliferation is increased and cell death is decreased compared to in wild-type mice

absent cerebellar foliation ( J:77123 )

• at P1

abnormal cerebellum external granule cell layer morphology ( J:77123 )

• thickened

Purkinje cell degeneration ( J:77123 )

ectopic Purkinje cell ( J:77123 )

• several Purkinje cells migrate towards the cerebellar surface and intermingle with granule cells

abnormal cerebellar molecular layer ( J:77123 )

• unlike in wild-type mice, mature granule cells are found within the molecular layer due to disrupted migration

abnormal cerebellum vermis morphology ( J:77123 )

• the cerebellar vermis is enlarged after 3 weeks

enlarged cerebellum ( J:77123 )

behavior/neurological

ataxia ( J:77123 )

• after 3 weeks mice exhibit ataxia that worsens until 8 weeks of age

impaired balance ( J:77123 )

• after 3 weeks

decreased locomotor activity ( J:77123 )

• after 3 weeks

neoplasm

neoplasm ( J:77123 )

N • despite the loss of Pten in several human tumors including glioblastoma, mice do not exhibit any neoplastic transformation

cellular

abnormal neuronal migration ( J:77123 )

• migration of Purkinje cells is impaired with the majority of cells clustering above the fourth ventricle without recognizable orientation

• Golgi, stellate, basket, Bergmann glial and oligodendrocyte cells fail to migrate properly and are randomly distributed throughout the cerebellum

Genotype
MGI:5293751

cn8

• Allelic Composition: Fbxw7^tm1.1Axbe/Fbxw7^tm1.1Axbe; Tg(En2-cre)22Alj/0
• Genetic Background: Not Specified

nervous system

nervous system phenotype ( J:176598 )

N • molecular layer structure is normal

abnormal neuron differentiation ( J:176598 )

• at E18.5, granule cell progenitors exhibit premature migration compared to in wild-type mice

abnormal cerebellar foliation ( J:176598 )

abnormal Purkinje cell morphology ( J:176598 )

• Purkinje cells are small, irregularly-shaped, less organized, more widely spread, and defective in arborization compared to in wild-type mice

decreased Purkinje cell number ( J:176598 )

• between P2, P7 and in the adult

decreased Purkinje cell size ( J:176598 )

abnormal cerebellum fissure morphology ( J:176598 )

• supranumeral fissures in the central lobes

cerebellum vermis hypoplasia ( J:176598 )

small cerebellum ( J:176598 )

• as early as P2

cellular

abnormal neuron differentiation ( J:176598 )

• at E18.5, granule cell progenitors exhibit premature migration compared to in wild-type mice