Animal models of lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC).
Animal models of lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC) are highly desired to enable detailed investigation of the pathogenesis of these diseases. Multiple rats and mice have been generated in which a mutation similar to that occurring in TSC patients is present in an allele of Tsc1 or Tsc2. Unfortunately, these mice do not develop pathologic lesions that match those seen in LAM or TSC. However, these Tsc rodent models have been useful in confirming the two-hit model of tumor development in TSC, and in providing systems in which therapeutic trials (e.g., rapamycin) can be performed. In addition, conditional alleles of both Tsc1 and Tsc2 have provided the opportunity to target loss of these genes to specific tissues and organs, to probe the in vivo function of these genes, and attempt to generate better models. Efforts to generate an authentic LAM model are impeded by a lack of understanding of the cell of origin of this process. However, ongoing studies provide hope that such a model will be generated in the coming years.
Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. dk@rics.bwh.harvard.edu
David J
DJ
Kwiatkowski
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018192:Lymphangioleiomyomatosis / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000378:metabolism / Q000473:pathology*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C000624653:TSC2 protein, human; C000624654:Tsc2 protein, mouse; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases