Students will experiment with an interactive animation to compare mutant and wild-type mice in a water maze. They will analyze data and discuss findings of a research paper.

In this activity students will watch an interactive animation of an experiment in which two types of mice are placed in a Morris water maze. One group of mice has a mutation in which a gene associated with memory and learning has been knocked out. They will be given the chance to analyze the results of the experiment. Next they be given data from an experiment with a different gene mutation and asked to make comparisons and draw conclusions. After analyzing these two experiments with the two different types of knockout mice the students will read a press release from the Welcome Sanger Trust Institute describing the findings in a paper published in the Journal of Neuroscience which describes these two experiments. This will help the students follow the levels of organization described in the G2C website as they move from the concept of a gene to that of cognition. National Science Standards Content Standard A: Science As Inquiry Abilities necessary to do scientific inquiry Understandings about scientific inquiry Content Standard C: Life Science The Cell The Behavior of Organisms Content Standard E: Science and Technology Understandings about nature and technology Science as a Human Endeavor Content Standard G: History and Nature of Science Nature of Scientific Knowledge Learning Goals and Objectives The students will be able to: 1. Formulate hypotheses 2. Summarize the conclusions of an experiment in which learning and memory are studied in wild type and mutant mice 3. Discover the way a scientist investigates a gene, the protein it produces and the behavior it leads to in mice as they learn a particular task. 4. Understand that the molecules of learning and memory and have been conserved by evolution. 5. Manipulate a protein alignment tool to compare the proteins produced by genes in a series of model organisms 6. Examine and create concept maps Assumptions of Prior Knowledge Students should have studied either introductory biology or introductory psychology at the high school level. Become familiar with, and learn how to navigate through, G2C online (www.g2conline.org). Misconceptions A gene will always produce the same protein in all organisms. A gene mutation in a mouse and a gene mutation in a human will always cause the same change in behavior Implementing the Lesson Become familiar with, and learn how to navigate through G2C online (http:www.g2conline.org/education.html) Time Two 45 minute periods Before class Photocopy Student worksheet 1 Make sure students have access to the internet During class In this activity the students will observe an on-line animation of an experiment dealing with the behavior of mice in a Morris Water Maze. This is a tool that is frequently used to test behavior related to learning in rodents. In this case two groups of mice are tested in their ability to locate an invisible escape platform. The time in which is takes to locate the platform and the swimming path are both measured. The experimental group of mice are known as knockout mice and have had a gene known as SAP-102 knocked out. This particular gene creates a protein that is important in nerve transmission across the synapse and has been associated with problems in learning. In the interactive animation the students will move the mice into the water maze and observe and record both the time and swimming path of the experimental mice and control mice (wild type) as they try to locate the platform. Students will fill in a worksheet as they make their observations and draw their conclusions. They will then be given data regarding another type of knockout mouse called PSD -95 and make comparisons in the behavior of the two types of mutant mice. after graphing a set of data describing swimming path length. A series of questions will be given for students to research to help them understand the science behind these experiments. They will then read a press release describing the results of these two experiments and learn what the actual investigators concluded from doing the actual experiments. Glossary Chimera- is an animal that has two or more different populations of genetically distinct cells that originated in different zygotes; if the different cells emerged from the same zygote, it is called a mosaicism. Cognition-is the term referring to the mental processes involved in gaining knowledge and comprehension, including thinking, knowing, remembering, judging and problem solving. DLG3- is a gene called Discs Large, Drosophila 3, located on the X-chromosome and in humans is linked to mental retardation. It encodes synapse-associated protein 102 and is also known as the SAP102 gene. The protein is a membrane associated guanylate kinase protein (MAGUK) located in synaptic junctions and associated with memory and learning. DNA-Deoxyribonucleic acid is a chemical found primarily in the nucleus of cells. DNA carries the genetic information for making all the structures and materials the body needs to function.,It is capable of self-replication and synthesis of RNA. Electrophysiology-The study of the mechanisms of production of electrical phenomena, particularly in the nervous system, and their consequences in the living organism Gene- The basic unit of inheritance. A gene is a segment of DNA that specifies the structure of a protein or an RNA molecule. Gene mutation-A change or alteration in a gene so that it does not work in the normal way. Mutations are changes to the base pair sequence of genetic material (either DNA or RNA). ... Knockout gene-A gene knockout is a genetic technique in which an organism is engineered to carry genes that have been made inoperative (have been "knocked out" of the organism). This is done for research purposes. Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function. Researchers draw inferences from the difference between the knockout organism and normal individuals. The term also refers to the process of creating such an organism, as in "knocking out" a gene. Morris Water Maze-a behavioral device used to investigate spatial learning and memory in laboratory rats, mice and other species. It consists of a large circular pool filled with opaque water in which a small escape platform is hidden. Neuroscience-Neuroscience is a field that is devoted to the scientific study of the nervous system. Such studies may include the structure, function, development, genetics, biochemistry, physiology, pharmacology, and pathology of the nervous system. ... Protein-A molecule composed of amino acids linked together in a particular order specified by a gene’s DNA sequence. Proteins perform a wide variety of functions including serving as enzymes, structural components or signaling molecules. Proteomics-An emerging field of science that focuses on the multitude of tasks assigned to proteins churned out by our genes. PSD-95- a gene that produces a protein which is a member-associated guanylate kinase located in synaptic junctions and may contribute to learning and memory. SAP102- a gene called synapse associated protein that produces a protein which is a member-associated guanylate kinase (MAGUK) located in synaptic junctions and may contribute to learning and memory. Also known as DLG3 Synapse-The junction between nerve cells where a nerve impulse is transferred from one neuron to another. X-linked-A trait or disease tied to genes on the X chromosome, which is one of the sex chromosomes that determine gender of an organism. Suggestions for Extended Learning 1. The SAP 102 mice are called knockouts. Please go to the section of the website called gene knockout and follow Dr. Seth Grant as he explains the process used to knockout a gene in mice. As you can see knocking out a gene is a very complicated process. Form groups and divide up the following questions. Each member of the group will research the answer to their particular question. They will become the “experts” in the class on that question. The “experts” will have the chance to meet to share their research. They will then report back to their original groups to explain the information they have discovered with the rest of the group. You can also visit the website called DNA interactive (www.dnai.org) for more information on this topic. Go to Applications, then to Genes and Medicine and then to Gene Targeting 1. What are some other uses of knockout mice? 2. What are the advantages and disadvantages of this technique? 3. Find out the difference between conventional knockouts and conditional knockouts or tissue specific gene targeting 4. How can gene targeting lead to possibilities for new therapies and correcting genetic defects? The class will then discuss the answers to the questions as a large group. 2. Create a concept map. Select 7 words from the glossary to use as your main concepts. Add any other words that you think are necessary. Refer to the rules for writing concept maps. View other maps on the website to help you. 3. Mice are one of several model organism used in science. Research some of the rules for using mice in a laboratory. Explain any ethical issues you may come across. Compare the rules for the use of animals in the laboratory in the United States versus the United Kingdom.

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