Disruption of laminin beta 2 chain production causes alterations in morphology and function in the CNS

From the elegant studies of Ramon y Cajal (1909) to the current advances in molecular cloning (e.g., Farber and Danciger, 1997), the retina has served as an ideal model for the entire CNS. We have taken advantage of the well described anatomy, physiology, and molecular biology of the retina to begin to examine the role of the laminins, one component of the extracellular ma trix, on the processes of neuronal differentiation and synapse formation in the CNS. We have examined the effect of the deletion of one laminin chain, the beta 2 chain, on retinal development. The gross development of retinas from laminin beta 2 chain-deficient animals appears normal, and photorecep tors are formed. However, these retinas exhibit several pathologies: lamini n beta 2 chain-deficient mice display abnormal outer segment elongation, ab normal electroretinograms, and abnormal rod photoreceptor synapses. Morphol ogically, the outer segments are reduced by 50% in length; the outer plexif orm layer of mutant animals is disrupted specifically, because only 7% of o bserved rod invaginating synapses appear normal, whereas the inner plexifor m layer is undisturbed; finally, the rate of apoptosis in the mutant photor eceptor layer is twice that of control mice. Physiologically, the electrore tinogram is altered; the amplitude of the b-wave and the slope of the b-wav e intensity-response function are both decreased, consistent with synaptic disruption in the outer retina. Together, these results emphasize the promi nence of the extracellular matrix and, in particular, the laminins in the d evelopment and maintenance of synaptic function and morphogenesis in the CN S.