Matthias W. Voigt, Jens Schepers, Jacqueline Haas, Oliver von Bohlen und Halbach

• Simple Summary Neurotrophins are growth factors that help the brain grow and function well. One of them is called brain-derived neurotrophic factor (BDNF). BDNF affects how much we weigh and how well we learn and remember things. There are mice with reduced levels of BDNF. Mice have been developed that do not express BDNF at all, but they die soon after they are born. So, mice that have only half of the normal BDNF level and mice that have very low BDNF levels in some brain cells, but normal BDNF levels in other brain cells, have been generated. Furthermore, it is possible to generate new mouse lines by breeding these two types of mice together. These new mice have very little BDNF in their brain. They are alive, but they weigh more and have smaller brains than normal mice. They also act differently, especially in how they move. Abstract Neurotrophins, which belong to the family of growth factors, not only play crucial roles during development but are also involved in many processes in the postnatal brain. One representative of neurotrophins is brain-derived neurotrophic factor (BDNF). BDNF plays a role in the regulation of body weight and neuronal plasticity and is, therefore, also involved in processes associated with learning and memory formation. Many of the studies on BDNF have been carried out using BDNF-deficient mice. Unfortunately, homozygous deletion of BDNF is lethal in the early postnatal stage, so heterozygous BDNF-deficient mice are often studied. Another possibility is the use of conditional BDNF-deficient mice in which the expression of BDNF is strongly downregulated in some brain cells, for example, in the neurons of the central nervous system, but the expression of BDNF in other cells in the brain is unchanged. To further reduce BDNF expression, we crossed heterozygous BDNF-deficient mice with mice carrying a deletion of BDNF in neurofilament L-positive neurons. These offspring are viable, and the animals with a strong reduction in BDNF in the brain show a strongly increased body weight, which is accompanied by a reduction in brain weight. In addition, these animals show behavioral abnormalities, particularly with regard to locomotion.