Phenotypes associated with this allele

• Allele Symbol: Anapc2^tm1Kna
• Allele Name: targeted mutation 1, Kim Nasmyth
• Allele ID: MGI:3029825
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Anapc2^tm1Kna/Anapc2^tm2Kna Tg(Mx1-cre)1Cgn/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3686618
cn2	Anapc2^tm1Kna/Anapc2^tm1Kna Tg(Ttr-cre/Esr1*)1Vco/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3686631

Genotype
MGI:3686618

cn1

• Allelic Composition: Anapc2^tm1Kna/Anapc2^tm2Kna; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

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

mortality/aging

premature death ( J:87782 )

• most die during the second week after the first pI/C injection to induce cre-mediated deletion of Anapc2 in the liver and lymphocytes

liver/biliary system

decreased liver glycogen level ( J:87782 )

• hepatocytes of mutants treated with pI/C lack glycogen

abnormal hepatocyte morphology ( J:87782 )

• hepatocytes are greatly enlarged, lack nuclear membranes, and contain condensed chromosomes in 6 of 10 mutants after pI/C injection

• 72% of mitotic hepatocytes are in a prometaphase-like state with condensed chromatin

abnormal liver physiology ( J:87782 )

• levels of the liver enzymes alanine aminotransferase and glutamate dehydrogenase are highly elevated in pI/C injected mutants, indicating functional impairment and damage of hepatocytes

increased hepatocyte proliferation ( J:87782 )

• quiescent hepatocytes of some but not all livers enter into a proliferative state, resulting in a mitotic arrest

• 2/3 hepatectomy in mutants transplanted with wild-type bone marrow and treated with pI/C caused 70% of hepatoctyes to re-enter the cell cycle and embark on proliferation and arrest in metaphase 3 to 5 days after hepatectomy

liver failure ( J:87782 )

• die from acute liver failure after pI/C injection

hematopoietic system

anemia ( J:87782 )

• the 4 of 10 mutants injected with pI/C with normal livers and 2 of 6 with abnormal livers show severe anemia

decreased hemoglobin content ( J:87782 )

• the 4 of 10 mutants injected with pI/C with normal livers show decreased hemoglobin levels

homeostasis/metabolism

increased circulating bilirubin level ( J:87782 )

• levels of bilirubin are highly elevated in pI/C injected mutants

abnormal enzyme/coenzyme level ( J:87782 )

• levels of the liver enzymes alanine aminotransferase and glutamate dehydrogenase are highly elevated in pI/C injected mutants, indicating functional impairment and damage of hepatocytes

decreased liver glycogen level ( J:87782 )

• hepatocytes of mutants treated with pI/C lack glycogen

skeleton

abnormal bone marrow morphology ( J:87782 )

• develop severe bone marrow aplasia within 4 days of pI/C injection; by day 4, majority of nucleated cells disappear from the bone marrow which contains mainly erythrocytes and a few lymphocytes

cellular

increased hepatocyte proliferation ( J:87782 )

• quiescent hepatocytes of some but not all livers enter into a proliferative state, resulting in a mitotic arrest

• 2/3 hepatectomy in mutants transplanted with wild-type bone marrow and treated with pI/C caused 70% of hepatoctyes to re-enter the cell cycle and embark on proliferation and arrest in metaphase 3 to 5 days after hepatectomy

Genotype
MGI:3686631

cn2

• Allelic Composition: Anapc2^tm1Kna/Anapc2^tm1Kna; Tg(Ttr-cre/Esr1*)1Vco/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

premature death ( J:87782 )

• 40% of mutants injected with 4-hydroxytamoxifen (4-OHT) to delete Anapc2 specifically in hepatocytes, die of liver failure within 2-3 weeks of the first injection

• surviving mutants subjected to 1/4 hepatectomy one month after the first 4-OHT injection, die from liver failure between 12-15 days after the hepatectomy, whereas controls survive

liver/biliary system

increased hepatocyte proliferation ( J:87782 )

• quiescent hepatocytes spontaneously enter the cell cycle and proliferate and arrest in a mitotic-like state

abnormal hepatocyte morphology ( J:87782 )

• hepatocytes are enlarged and arrested in metaphase in mutants treated with 4-OHT to delete Anapc2 in hepatocytes

liver failure ( J:87782 )

• 40% of mutants injected with 4-OHT to delete Anapc2 specifically in hepatocytes, die of liver failure within 2-3 weeks of the first injection

cellular

increased hepatocyte proliferation ( J:87782 )

• quiescent hepatocytes spontaneously enter the cell cycle and proliferate and arrest in a mitotic-like state