Phenotypes associated with this allele

• Allele Symbol: Tg(Rnu6-RNAi:Bccip)4Zshn
• Allele Name: transgene insertion 4, Zhiyuan Shen
• Allele ID: MGI:5288517
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(Rnu6-RNAi:Bccip)4Zshn/0	FVB/N-Tg(Rnu6-RNAi:Bccip)4Zshn	MGI:5292119
cn2	Tg(EIIa-cre)C5379Lmgd/0 Tg(Rnu6-RNAi:Bccip)4Zshn/0 Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:5292118
cn3	Tg(EIIa-cre)C5379Lmgd/0 Tg(Rnu6-RNAi:Bccip)4Zshn/0	involves: C57BL/6 * FVB/N	MGI:5292117
tg4	Tg(Rnu6-RNAi:Bccip)4Zshn/Tg(Rnu6-RNAi:Bccip)4Zshn	FVB/N-Tg(Rnu6-RNAi:Bccip)4Zshn	MGI:5292129

Genotype
MGI:5292119

cn1

• Allelic Composition: Tg(Rnu6-RNAi:Bccip)4Zshn/0
• Genetic Background: FVB/N-Tg(Rnu6-RNAi:Bccip)4Zshn

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

cellular

increased cellular sensitivity to gamma-irradiation ( J:176115 )

• retroviral cre-induced mutant MEFs show greater growth inhibition in response to gamma-irradiation (1-4 Gy) compared to control cells

• after irradiation, knockdown MEFs show a significantly higher level of sister chromatid unions (SCU) than control cells; other forms of chromosome damage are not significantly different from controls; at 8 hours, significantly more chromosomal aberrations (SCU) remain in mutant MEFs indicating impaired repair processes

decreased cell proliferation ( J:176115 )

• cultured MEFs infected with a retroviral cre increase in number more slowly and display more DNA damage markers than MEFs transfected with a retroviral reporter

• after treatment with alphidicolin, cells display lower incorporation of BrdU than control MEFs

abnormal double-strand DNA break repair ( J:176115 )

• 4 and 8 hours after irradiation, double strand break (DSB) repair, assessed by presence of gammaH2AX foci, is impaired in Bccip knockdown (cre treated) MEFs compared with control cells (many more foci are observed indicating inefficient repair of breaks)

• numbers of Rad51 foci are reduced after 2 Gy of irradiation compared to number detected in irradiated wild-type cells

chromosomal instability ( J:176115 )

• Bccip MEFs infected with a retroviral cre vector show significantly higher levels of spontaneous chromosome breakage (single chromatid breaks with unpaired fragments, paired sister chromatid fragments (pSCF) and sister chromatid unions (SCU)) than control MEF cultures; level of sister chromatid exchanges (SCE) is only modestly elevated

homeostasis/metabolism

abnormal double-strand DNA break repair ( J:176115 )

• 4 and 8 hours after irradiation, double strand break (DSB) repair, assessed by presence of gammaH2AX foci, is impaired in Bccip knockdown (cre treated) MEFs compared with control cells (many more foci are observed indicating inefficient repair of breaks)

• numbers of Rad51 foci are reduced after 2 Gy of irradiation compared to number detected in irradiated wild-type cells

Genotype
MGI:5292118

cn2

• Allelic Composition: Tg(EIIa-cre)C5379Lmgd/0; Tg(Rnu6-RNAi:Bccip)4Zshn/0; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

mortality/aging

embryonic lethality ( J:176115 )

• Trp53 deficiency does not result in significant rescue of the embryonic lethality seen in Bccip deficiency; ratio of viable double transgenic to wild-type offspring is not increased in the Trp53-null or heterozygous background

Genotype
MGI:5292117

cn3

• Allelic Composition: Tg(EIIa-cre)C5379Lmgd/0; Tg(Rnu6-RNAi:Bccip)4Zshn/0
• Genetic Background: involves: C57BL/6 * FVB/N

mortality/aging

embryonic lethality during organogenesis ( J:176115 )

• lethality occurs before E11.5

growth/size/body

embryonic growth retardation ( J:176115 )

• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls

• embryos at E7.5 and E8.5 show significant developmental retardation

embryo

increased embryonic tissue cell apoptosis ( J:176115 )

• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls

decreased inner cell mass proliferation ( J:176115 )

• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)

abnormal embryo development ( J:176115 )

abnormal mesoderm development ( J:176115 )

• no mesoderm differentiation is apparent at E7.5

embryonic growth arrest ( J:176115 )

• developmental arrest is observed at E11.5

embryonic growth retardation ( J:176115 )

• significant delay and abnormal development is observed at E6.5, evidenced by abnormal mass of embryonic tissues relative to controls

• embryos at E7.5 and E8.5 show significant developmental retardation

absent neural plate ( J:176115 )

• development of the neural plate is not evident at E8.5

absent notochord ( J:176115 )

• development of the notochord is not evident at E8.5

absent amniotic cavity ( J:176115 )

• amniotic cavity does not develop

cellular

increased embryonic tissue cell apoptosis ( J:176115 )

• elevated apoptosis is observed by E7.5 in mutant embryos, but at E6.5 there is little difference compared to controls

decreased cell proliferation ( J:176115 )

• the proliferation index of cells in embryonic tissues is slightly reduced at E6.5 relative to controls and reduction is significant by E7.5

decreased inner cell mass proliferation ( J:176115 )

• growth of the inner cell mass is impaired in cultured mutant blastocysts compared to wild-type starting at culture day 3 (equivalent to E6.5 in vivo)

nervous system

absent neural plate ( J:176115 )

• development of the neural plate is not evident at E8.5

reproductive system

decreased litter size ( J:176115 )

• litters are significantly smaller (5.1 pups/litter) than wild-type controls (10.3/litter)

• the number of double-positive transgenic offspring is greatly reduced, but some are viable; however, some of these animals were shown to have lost the RNAi cassette spontaneously

Genotype
MGI:5292129

tg4

• Allelic Composition: Tg(Rnu6-RNAi:Bccip)4Zshn/Tg(Rnu6-RNAi:Bccip)4Zshn
• Genetic Background: FVB/N-Tg(Rnu6-RNAi:Bccip)4Zshn

normal phenotype

no abnormal phenotype detected ( J:176115 )

• mice are viable, fertile and have same lifespan as wild-type