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The whole thing starts with Ginny and Janis, two teenage girls. They are best friends. Ginny traditionally has bad luck dating, as we see when her date dies in a mousetrap.
After Ginny and Janis, we meet Al, who is a boy-genius. Because Al is so smart, he's in highschool despite only being a kid. Al gets abducted by the government and asked by the Prez, Tex, to build a better mousetrap to use on the mice across the hall who are suspected of developing mousetraps of mass destruction. Al has a hard time deciding whether or not to build weapons for the government. While trying to decide, Al meets Jive, a self-proclaimed "coolest guy ever". Jive, Ginny, and Janis, help Al realize he doesn't want to use his intelligence to hurt other mice.
One day, the little boy who's bedroom the mice all live in, gets a pet mouse, Pierre. Pierre meets Ginny and Janis and tells them he has never been free. The government brands Pierre a terrorist simply because he lives in a cage. Janis decides they need to find a way to free Pierre. Janis, along with Ginny, Al, and Jive, start to make plans. Ginny goes to tell Pierre about the impending jail break, letting it slip that Janis likes Pierre. You know, "likes" likes. As Ginny is walking back to her friends, she runs into Janis's exboyfriend, D-Con. D-Con is a rat who was thought to have died when he fell on a mousetrap. Ginny had witnessed his supposed death because D-Con was trying to hurt her after over-hearing him talk about an actual terror plot with his accomplice, the cat. D-Con and Janis reunite. This causes a rift between Ginny and Janis. D-Con goes to Pierre's cage to use him as a scape-goat for his terror plan, but Jive kung-fu fights with him until Janis gets there. Janis sees D-Con for what he truly is and kicks him in the nads, which sends him tumbling off the table and onto a rat trap, killing him for real.
Janis feels betrayed and alone after all that happened and simply can't help Pierre at this point. Pierre says it's okay, because he has an imaginary friend, Ted, to keep him company. Everyone can see Ted because Pierre has a very active imagination.
Ginny's mom makes her take ballet, where she meets Chuck.
After talking to a disillusioned Janis, Jive decides to run for Prez. When Ginny sees this news, she figures Janis is behind it. Ginny confronts Janis and they reconcile.
Schmoikel, a schrew, moves in and starts to go to school with the other mice. The teacher assigns Chuck as his lab partner to help him get up to speed.
Janis's cousin, Dixie, arrives just in time to participate in a Pop Music contest, called Mouse Idol. Dixie's dream is to be a pop star. Dixie wins the competition, mostly because she's got big boobs.
Meanwhile, Jive appoints Janis as his campaign manager.
Al's parents, who are clearly clueless about what their child likes, decide that Al needs to spend more time with kids his own age. Thus, they send Al to camp, where he meets Ben, the Scout Leader. During a camping trip in the hallway, Ben sacrifices most of his tail fighting off the cat so the kids can escape.
Carry Johnson asks Jive to be his running mate, and suddenly Jive is the vice-presidential candidate for a major party. The election is close, but Tex wins and decides he is now the mice new god-king.
Dixie, needing angst to write her songs, moves in with Janis, much to Janis's dismay. This only lasts a few weeks, because Janis gets accepted into college early. Janis moves away from the little boy's bedroom into the little girl's bedroom next door.
Pierre and Ted wake up one day to find a strange box in their cage. Inside is another mouse, Bulbina. She doesn't speak any language they know. Pierre asks Al to build a translation device for them to use. Meanwhile, Scout Leader Ben, who Ginny has a crush on, comes to Al asking to build a prosthetic tail. An overworked Al accidentally puts the AI module from the translator into the tail. The bionic tail takes over Ben's body and goes on a rampage, taking Ginny prisoner. Schmoikel leads a group of super-hero wannabes to fight the tail. This gives Al an idea. The group graps the tail and tickles the host into submission. Ted cuts off the tail, which then attempts a getaway with Ted still hanging on. This leads them back to Pierre's cage where a crazed Bulbina rams through the glass to attack Ginny. Ted and the tail crash into Bulbina, which sends Bulbina and the tail through the window, never to be seen again.
Pierre is now free and is unsure what to do with his freedom. Pierre and Ted decide to try to find Janis in the room next door, but take a wrong turn.
A bully starts to take Al's lunch money. Janis comes home on break and together with Ginny try to help Al solve his bully problem.