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Alzheimer’s disease, amyotrophic lateral sclerosis, and transgenic mice
  1. N P S BAJAJ,
  2. N G IRVING,
  3. P N LEIGH,
  1. Departments of Neuroscience and Clinical Neurosciences
  2. The Institute of Psychiatry
  3. De Crespigny Park
  4. Denmark Hill
  5. London, UK
  1. Dr N P S Bajaj, Department of Clinical Neurosciences, The Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. Telephone: 0044 171 919 3402; fax 0044 171 708 0017; email spgtnpb{at}

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Transgenic mouse technology has contributed much to our understanding of the function and dysfunction of the nervous system. It has helped us to model and test hypotheses relating to neurodegenerative diseases, such as Alzheimer’s disease and motor neuron disease, and has also provided insight into the molecular basis of higher brain functions such as learning and memory.

Alteration of the mouse genome is carried out by one of two methods: the first involves the addition of new genes (known as transgenes) and the second involves the modification of endogenous mouse genes. The first method usually involves microinjection of the recombinant DNA into the pronucleus of a one cell mouse embryo. The resulting manipulated embryos are reimplanted into the oviducts of a pseudopregnant female mouse and the offspring are then screened for the presence of the transgene so as to identify transgenic progeny. The frequency of production of successful transgenic progeny by this method is surprisingly good with a rate of about one in five to six offspring being transgenic.

Manipulation of endogenous mouse genes is a more complex process and involves the use of embryonic stem cells. Embryonic stem cells are derived from the inner cell mass of blastocysts, and retain the ability to differentiate into any cell type of the original mouse. Embryonic stem cells can be expanded in vitro and transfected so as to introduce new DNA. To generate transgenic mice, the modified embryonic stem cells cells are injected into host blastocysts and the resulting embryos are then reintroduced into the reproductive tracts of pseudopregnant females. Animals derived from these manipulated blastocysts are chimeric—that is, some of their cells are derived from the inner cell mass of the host blastocyst and some from the injected embryonic stem cells. Coat colour is often used to identify such chimeric animals. …

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