All Phenotypes Orc1<tm1.1Gle> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Orc1^tm1.1Gle
targeted mutation 1.1, Gustavo Leone
MGI:6355393

Summary

8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Orc1^tm1.1Gle/Orc1^tm1.1Gle	involves: C57BL/6 * SJL	MGI:6388689
cn2	Orc1^tm1.1Gle/Orc1^tm1.1Gle Alb^{tm1(cre/ERT2)Mtz}/Alb⁺	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:7408241
cn3	Orc1^tm1.1Gle/Orc1^tm1.1Gle Tg(Cyp1a1-cre)1Dwi/0	involves: C57BL/6 * CBA * SJL	MGI:7408229
cn4	Orc1^tm1.1Gle/Orc1^tm1.2Gle Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺	involves: C57BL/6 * CBA * SJL	MGI:7408228
cn5	Orc1^tm1.1Gle/Orc1^tm1.2Gle Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: C57BL/6 * DBA * SJL	MGI:7408239
cn6	Orc1^tm1.1Gle/Orc1^tm1.1Gle Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: C57BL/6 * DBA * SJL	MGI:6388690
cn7	Orc1^tm1.1Gle/Orc1^tm1.1Gle Prl2c2^tm1(cre)Gle/Prl2c2⁺	involves: C57BL/6 * SJL	MGI:6388638
cn8	Orc1^tm1.1Gle/Orc1^tm1.2Gle Prl2c2^tm1(cre)Gle/Prl2c2⁺	involves: C57BL/6 * SJL	MGI:7408236

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.1Gle
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)

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

cellular

polyploidy ( J:272584 )

• mouse embryonic fibroblasts (MEFs) infected with a Cre-expressing retrovirus accumulate greater than 2C DNA content

absent fibroblast proliferation ( J:272584 )

• MEFs infected with a Cre-expressing retrovirus cease to proliferate and show negligible BrdU incorporation relative to control MEFs

decreased DNA replication ( J:272584 )

• MEFs infected with a Cre-expressing retrovirus exhibit a block in DNA replication leading to S-phase arrest

homeostasis/metabolism

decreased DNA replication ( J:272584 )

• MEFs infected with a Cre-expressing retrovirus exhibit a block in DNA replication leading to S-phase arrest

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.1Gle Alb^{tm1(cre/ERT2)Mtz}/Alb⁺
Genetic Background	involves: 129S2/SvPas * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alb^{tm1(cre/ERT2)Mtz} mutation (1 available); any Alb mutation (91 available)
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)

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

liver/biliary system

liver/biliary system phenotype ( J:272584 )

N	• mice fed tamoxifen chow at 6 weeks of age (postweaning) show no significant differences in hepatocyte nuclear size or ploidy levels at 9 weeks of age relative to controls

increased hepatocyte karyomegaly ( J:272584 )

• mice fed tamoxifen chow at birth (preweaning) exhibit livers with fewer hepatocytes containing visibly larger nuclei at 3 weeks of age

decreased hepatocyte number ( J:272584 )

• mice fed tamoxifen chow at birth (preweaning) exhibit livers with fewer hepatocytes at 3 weeks of age

cellular

cellular phenotype ( J:272584 )

N	• mice fed tamoxifen chow at 6 weeks of age (postweaning) show no significant differences in hepatocyte ploidy levels at 9 weeks of age relative to controls

polyploidy ( J:272584 )

• mice fed tamoxifen chow at birth (preweaning) exhibit hepatocytes accumulating 4C or greater DNA content by 3 weeks of age

increased hepatocyte karyomegaly ( J:272584 )

• mice fed tamoxifen chow at birth (preweaning) exhibit livers with fewer hepatocytes containing visibly larger nuclei at 3 weeks of age

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.1Gle Tg(Cyp1a1-cre)1Dwi/0
Genetic Background	involves: C57BL/6 * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Tg(Cyp1a1-cre)1Dwi mutation (1 available)

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

digestive/alimentary system

increased small intestinal crypt cell apoptosis ( J:272584 )

• the number of cleaved CASPASE-3-positive small intestine crypt cells is increased at 0, 2, 4, and 7 days after beta-napthoflavone (betaNF) treatment

abnormal small intestinal crypt cell proliferation ( J:272584 )

• the number of BrdU-positive small intestine crypt cells is reduced at day 2 but increased by day 4 post-betaNF treatment

• similarly, the number of BrdU/Krt8-double positive crypt cells per small intestine length is reduced at day 2 but increased by day 4 post-betaNF treatment

abnormal small intestine morphology ( J:272584 )

• at day 2 after the last of 5 consecutive beta-napthoflavone (betaNF) injections, small intestine architecture is severely disrupted, with fewer and smaller crypts and shorter, hypocellular and progressively disorganized villi

• however, by day 4 after the last betaNF injection, ORC1 protein levels are restored to nearly normal levels and a 4- to 5-day repopulation period ensues with enhanced DNA replication, progenitor cell proliferation and crypt hypertrophy such that crypt-villus integrity is fully restored at day 7 post-treatment

abnormal small intestine crypts of Lieberkuhn morphology ( J:272584 )

• at day 2 post-betaNF treatment, fewer and smaller crypts are observed in the small intestine

• however, crypt integrity is fully restored at day 7 post-betaNF treatment

abnormal small intestinal villus morphology ( J:272584 )

• at day 2 post-betaNF treatment, small intestine villi are shorter, hypocellular and progressively disorganized

• however, villus integrity is fully restored at day 7 post-betaNF treatment

decreased small intestinal villus height ( J:272584 )

• small intestine villi are shorter at day 2 but not at day 7 post-betaNF treatment

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:272584 )

• at day 2 post-betaNF treatment, fewer and smaller crypts are observed in the small intestine

• however, crypt integrity is fully restored at day 7 post-betaNF treatment

cellular

increased small intestinal crypt cell apoptosis ( J:272584 )

• the number of cleaved CASPASE-3-positive small intestine crypt cells is increased at 0, 2, 4, and 7 days after beta-napthoflavone (betaNF) treatment

abnormal small intestinal crypt cell proliferation ( J:272584 )

• the number of BrdU-positive small intestine crypt cells is reduced at day 2 but increased by day 4 post-betaNF treatment

• similarly, the number of BrdU/Krt8-double positive crypt cells per small intestine length is reduced at day 2 but increased by day 4 post-betaNF treatment

increased DNA replication ( J:272584 )

• DNA replication is enhanced during the 4- to 5-day repopulation period that follows after acute disruption of intestinal integrity

homeostasis/metabolism

increased DNA replication ( J:272584 )

• DNA replication is enhanced during the 4- to 5-day repopulation period that follows after acute disruption of intestinal integrity

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.2Gle Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
Genetic Background	involves: C57BL/6 * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Edil3^{Tg(Sox2-cre)1Amc} mutation (5 available); any Edil3 mutation (42 available)
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1^tm1.2Gle mutation (0 available); any Orc1 mutation (60 available)

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

mortality/aging

embryonic lethality, complete penetrance ( J:272584 )

• no live mice are recovered at E10.5 or at 2 weeks of age

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.2Gle Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: C57BL/6 * DBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1^tm1.2Gle mutation (0 available); any Orc1 mutation (60 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

liver/biliary system

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks of age, hepatocytes are strikingly larger with larger nuclei than controls

decreased hepatocyte number ( J:272584 )

• fewer hepatocytes are observed relative to controls

• however, liver gross morphology is normal from 3 weeks to 3 months and liver to body weight ratios remain normal up to 6 months of age

cellular

polyploidy ( J:272584 )

• at 3 weeks of age, an increased proportion of hepatocytes with 4C DNA content is observed

• by 3 months of age, a larger proportion of hepatocytes with 8C or greater DNA content is observed

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks of age, hepatocytes are strikingly larger with larger nuclei than controls

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely

homeostasis/metabolism

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.1Gle Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: C57BL/6 * DBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

liver/biliary system

liver/biliary system phenotype ( J:272584 )

N	• mice exhibit normal liver regeneration at 36 h and 4 d after partial hepatectomy, with a comparable restoration of liver size, reduction in hepatocyte cell density, and increase in hepatocyte proliferation and DNA content within the regenerating lobe relative to controls

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks and 3 months of age, hepatocytes are strikingly larger with larger nuclei than controls

increased hepatocyte proliferation ( J:272584 )

• in keeping with precocious endoreduplication, the number of Ki-67-, BrdU-, and P-H3-positive (Ser10 and Ser28) hepatocytes is dramatically increased at 6 weeks of age

decreased hepatocyte number ( J:272584 )

• fewer hepatocytes are observed relative to controls

• however, liver gross morphology and liver to body weight ratios are normal from 1 week to 12 months of age

cellular

polyploidy ( J:272584 )

• at 3 months of age, an increased proportion of hepatocytes with 8C and 16C DNA content is observed

• livers begin to endoreduplicate hepatocyte genomes prematurely (by 1 week of age) and reach maximum ploidy by 6 months of age, well in advance of controls

increased hepatocyte karyomegaly ( J:272584 )

• at 3 weeks and 3 months of age, hepatocytes are strikingly larger with larger nuclei than controls

increased hepatocyte proliferation ( J:272584 )

• in keeping with precocious endoreduplication, the number of Ki-67-, BrdU-, and P-H3-positive (Ser10 and Ser28) hepatocytes is dramatically increased at 6 weeks of age

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely, accumulating equal to or greater than 8C DNA content prior to weaning

homeostasis/metabolism

abnormal DNA replication ( J:272584 )

• hepatocytes endoreduplicate their genomic DNA prematurely, accumulating equal to or greater than 8C DNA content prior to weaning

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.1Gle Prl2c2^tm1(cre)Gle/Prl2c2⁺
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Prl2c2^tm1(cre)Gle mutation (0 available); any Prl2c2 mutation (24 available)

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

normal phenotype

no abnormal phenotype detected ( J:272584 )

• E10.5 embryos are viable and live mice are recovered at 3 weeks of age; placentae appear histologically normal and show no major alterations in trophoblast giant cell (TGC) endoreduplication, as determined by the nuclear size, genomic DNA content, BrdU incorporation and Ccna2 expression in E10.5 TGCs

Allelic Composition	Orc1^tm1.1Gle/Orc1^tm1.2Gle Prl2c2^tm1(cre)Gle/Prl2c2⁺
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1^tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1^tm1.2Gle mutation (0 available); any Orc1 mutation (60 available)
Prl2c2^tm1(cre)Gle mutation (0 available); any Prl2c2 mutation (24 available)

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

normal phenotype

no abnormal phenotype detected ( J:272584 )

• placental development is normal, embryos are carried to term and all pups born exhibit no apparent abnormalities

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