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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Orc1tm1.1Gle
targeted mutation 1.1, Gustavo Leone
MGI:6355393
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
 		Orc1tm1.1Gle/Orc1tm1.1Gle involves: C57BL/6 * SJL MGI:6388689
cn2
 		Orc1tm1.1Gle/Orc1tm1.1Gle
Albtm1(cre/ERT2)Mtz/Alb+ 		involves: 129S2/SvPas * C57BL/6 * SJL MGI:7408241
cn3
 		Orc1tm1.1Gle/Orc1tm1.1Gle
Tg(Cyp1a1-cre)1Dwi/0 		involves: C57BL/6 * CBA * SJL MGI:7408229
cn4
 		Orc1tm1.1Gle/Orc1tm1.2Gle
Edil3Tg(Sox2-cre)1Amc/Edil3+ 		involves: C57BL/6 * CBA * SJL MGI:7408228
cn5
 		Orc1tm1.1Gle/Orc1tm1.2Gle
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+ 		involves: C57BL/6 * DBA * SJL MGI:7408239
cn6
 		Orc1tm1.1Gle/Orc1tm1.1Gle
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+ 		involves: C57BL/6 * DBA * SJL MGI:6388690
cn7
 		Orc1tm1.1Gle/Orc1tm1.1Gle
Prl2c2tm1(cre)Gle/Prl2c2+ 		involves: C57BL/6 * SJL MGI:6388638
cn8
 		Orc1tm1.1Gle/Orc1tm1.2Gle
Prl2c2tm1(cre)Gle/Prl2c2+ 		involves: C57BL/6 * SJL MGI:7408236


Genotype
MGI:6388689
cn1
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.1Gle
Genetic
Background		 involves: C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle 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




Genotype
MGI:7408241
cn2
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.1Gle
Albtm1(cre/ERT2)Mtz/Alb+
Genetic
Background		 involves: 129S2/SvPas * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Albtm1(cre/ERT2)Mtz mutation (2 available); any Alb mutation (97 available)
Orc1tm1.1Gle 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




Genotype
MGI:7408229
cn3
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.1Gle
Tg(Cyp1a1-cre)1Dwi/0
Genetic
Background		 involves: C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Tg(Cyp1a1-cre)1Dwi mutation (2 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




Genotype
MGI:7408228
cn4
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.2Gle
Edil3Tg(Sox2-cre)1Amc/Edil3+
Genetic
Background		 involves: C57BL/6 * CBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Edil3Tg(Sox2-cre)1Amc mutation (5 available); any Edil3 mutation (43 available)
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1tm1.2Gle 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




Genotype
MGI:7408239
cn5
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.2Gle
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+
Genetic
Background		 involves: C57BL/6 * DBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1tm1.2Gle mutation (0 available); any Orc1 mutation (60 available)
Speer6-ps1Tg(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




Genotype
MGI:6388690
cn6
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.1Gle
Speer6-ps1Tg(Alb-cre)21Mgn/Speer6-ps1+
Genetic
Background		 involves: C57BL/6 * DBA * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Speer6-ps1Tg(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




Genotype
MGI:6388638
cn7
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.1Gle
Prl2c2tm1(cre)Gle/Prl2c2+
Genetic
Background		 involves: C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Prl2c2tm1(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




Genotype
MGI:7408236
cn8
Allelic
Composition		 Orc1tm1.1Gle/Orc1tm1.2Gle
Prl2c2tm1(cre)Gle/Prl2c2+
Genetic
Background		 involves: C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Orc1tm1.1Gle mutation (0 available); any Orc1 mutation (60 available)
Orc1tm1.2Gle mutation (0 available); any Orc1 mutation (60 available)
Prl2c2tm1(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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Send questions and comments to User Support. 		last database update
11/12/2024
MGI 6.24 		The Jackson Laboratory