Urea Cycle Disorders Models

The urea cycle functions to eliminate excess nitrogen from the body. When this cycle is impaired, patients, usually neonates, develop diseases marked by severe hyperammonemia due to congenital or secondary defects in the metabolic enzymes or transporters within the urea cycle (urea synthesis pathway). The incidence rate of such disorders is 1 in 8,000.

● Induced Urea Cycle Disorders Mouse Models

Strain Name	Strain Type	Description
T014667 Arg1-flox × T050182 Rosa26-SA-CreERT2	Inducible, systemic conditional knock-out	Serum ammonia is significantly elevated 15 days after tamoxifen induction in 9-week-old Arg1 systemic conditional knockout mice, suggesting the arginase deficiency-like phenotype. The majority of conditional knockout mice do not survive beyond 21 days post-induction
T015076 Otc-flox × T050182 Rosa26-SA-CreERT2	Inducible, systemic conditional knock-out	Serum ammonia is significantly elevated 22 days after tamoxifen induction in 6-week-old Otc systemic conditional knockout mice, suggesting an ornithine transcarbamylase deficiency-like phenotype. Otc conditional knock-out mice begin to lose weight 19 days after induction, and the majority of conditional knockout mice die before 27 days after induction

T014667 Arg1-flox × T050182 Rosa26-SA-CreER^T2 (Systemic conditional Arg1 knock-out mice)

1. Arg1 protein expression

After tamoxifen injection, the expression of Arg1 protein was significantly decreased in the liver of Arg1-flox FL/FL, Rosa26-SA-CreER^T2 KI/WT mice.

2. Serum ammonia levels

One hundred mg/kg/d tamoxifen was injected into 9-week-old mice. The first day of injection was denoted as Day 1. Serum ammonia level were remarkably increased in Arg1-flox FL/FL, Rosa26-SA-CreER^T2 KI/WT mice at Day15.

3. Body weight and survival analysis

Three of 6 Arg1-flox FL/FL, Rosa26-SA-CreER^T2 KI/WT male mice died at Day 16, while 6 of 6 Arg1-flox FL/FL, Rosa26-SA-CreER^T2 KI/WT female mice died at Day 21. The remaining male mice were euthanized at 21 days.

T015076 Otc-flox × T050182 Rosa26-SA-CreER^T2 (Systemic conditional Otc knock-out mice)

1. Otc protein expression

After tamoxifen injection, expression of OTC protein is significantly decreased in the liver of Otc-flox FL/Y, Rosa26-SA-CreER^T2 KI/WT male mice and Otc-flox FL/FL, Rosa26-SA-CreER^T2 KI/WT female mice.

2. Plasma ammonia

One hundred mg/kg/d tamoxifen is injected into 6-week-old mice for deletion of the floxed region. The injection was performed on Day 1. Plasma ammonia levels of OTCD mice are significantly increased at Day 22. * comparison between male mice, # comparison between female mice.

3. Body weight and Survival analysis

Body weight of both male and female OTCD model mice begins to decrease on Day 19.