Rat and Mouse Models of Tuberous Sclerosis

Kwiatkowski, David J.

doi:10.1002/9783527630073.ch7

Cited by 1 publication

(1 citation statement)

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“…Using those animal models, embryonic lethality of homozygous mutants of TSC genes was shown, and various cell lines deficient for TSC genes were established. In addition, several tissue‐specific conditional gene‐targeting systems have been established . Although the detailed explanation of each system is beyond the scope of this review, suffice it to say that the functions of TSC genes in various tissues and recapitulation of TSC‐related pathology, especially for brain lesions, have been documented using such conditional knockout systems …”

Section: Tsc: a Multi‐organ Disorder With A Defect In The Tumor Supprmentioning

confidence: 99%

Mourning Dr. Alfred G. Knudson: the two‐hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex

Hino

Kobayashi

2017

Cancer Science

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On July 10, 2016, Alfred G. Knudson, Jr., MD, PhD, a leader in cancer research, died at the age of 93 years. We deeply mourn his loss. Knudson's two‐hit hypothesis, published in 1971, has been fundamental for understanding tumor suppressor genes and familial tumor‐predisposing syndromes. To understand the molecular mechanism of two‐hit‐initiated tumorigenesis, Knudson used an animal model of a dominantly inherited tumor, the Eker rat. From the molecular identification of Tsc2 germline mutations, the Eker rat became a model for tuberous sclerosis complex (TSC), a familial tumor‐predisposing syndrome. Animal models, including the fly, have greatly contributed to TSC research. Because the product of the TSC2/Tsc2 gene (tuberin) together with hamartin, the product of another TSC gene (TSC1/Tsc1), suppresses mammalian/mechanistic target of rapamycin complex 1 (mTORC1), rapalogs have been used as therapeutic drugs for TSC. Although significant activity of these drugs has been reported, there are still problems such as recurrence of residual tumors and adverse effects. Recent studies indicate that there are mTORC1‐independent signaling pathways downstream of hamartin/tuberin, which may represent new therapeutic targets. The establishment of cellular models, such as pluripotent stem cells with TSC2/Tsc2 gene mutations, will facilitate the understanding of new aspects of TSC pathogenesis and the development of novel treatment options. In this review, we look back at the history of Knudson and animal models of TSC and introduce recent progress in TSC research.

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Section: Tsc: a Multi‐organ Disorder With A Defect In The Tumor Supprmentioning

confidence: 99%