Lifespan and Incidence of Cancer and Other Diseases in Selected Long-Lived Inbred Mice and Their F1 Hybrids2

Smith, George S.; Walford, Roy L.; Mickey, M. R.

doi:10.1093/jnci/50.5.1195

Cited by 160 publications

(71 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Groups of mice were sacrificed at specified times and necropsies were performed. Inbred mouse strains differ in their sensitivities to spontaneous and carcinogen-induced tumor formation, and the mice used in our study (all from the same mixed C57BL/6 and 129 genetic background) were derived from tumorresistant parental strains (Malkinson and Beer, 1983;Smith et al, 1973).…”

Section: Resultsmentioning

confidence: 99%

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

et al. 2002

View full text Add to dashboard Cite

Events that contribute to tumor formation include mutations in the ras gene and loss or inactivation of cell cycle inhibitors such as p21 Cip1 and p27 Kip1 . In our previous publication, we showed that mice expressing the MMTV/v-Ha-ras transgene developed tumors earlier and at higher multiplicities in the absence than in the presence of p21 Cip1 . To further evaluate the combinatorial role of genetic alterations and loss of cell cycle inhibitors in tumorigenesis, we performed two companion studies. In the first study, wild type and p21 Cip1 -null mice were exposed to the chemical carcinogen, urethane. Similar to its effects in v-Ha-ras mice, loss of p21 Cip1 accelerated tumor onset and increased tumor multiplicity in urethane-treated mice. Lung tumors were the predominant tumor type in urethane-treated mice regardless of p21 Cip1 status. In the second study, tumor formation was monitored in v-Ha-ras mice expressing or lacking p27 Kip1 . Unlike p21 Cip1 , the absence of p27 Kip1 had no effect on the timing or multiplicity of tumor formation, which was largely restricted to mammary and salivary glands. However, once tumors appeared, they grew faster in p27 Kip1 -null mice than in p27 Kip1 -wild type mice. Increases in growth rate were particularly striking for salivary tumors in ras/p27 7/7 mice. Loss of p21 Cip1 , on the other hand, had no effect on tumor growth rate in v-Ha-ras mice. Collectively, our data suggest that p21 Cip1 suppresses tumor formation elicited by multiple agents and that p21 Cip1 and p27 Kip1 suppress tumor formation in different ways.

show abstract

Section: Resultsmentioning

confidence: 99%

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

et al. 2002

View full text Add to dashboard Cite

show abstract

“…C57BL/6 mice have a high incidence of late life l y m p h~m a ,~~.~~ but lymphoma is relatively rare in DBA/2J mice. 24 The relatively high incidence of lymphoma in our 4WC population may reflect, in part, the genetic contribution from the two high-lymphoma grandparents, and life span studies are now in progress with other 4WC populations to address this issue. However, both the incidence and the latency of mouse lymphomas are under complex control of multiple nondominant genes, including alleles of H-2, Fv-I and Fv-2, RCS-1, and other less well-characterized loci.…”

Section: Aging and Disease In Genetically Heterogeneous Micementioning

confidence: 97%

Lifespan and Lesions in Genetically Heterogeneous (Four-way Cross) Mice: A New Model for Aging Research

et al. 1996

View full text Add to dashboard Cite

Abstract. Genetically heterogeneous animal models provide many advantages for research on aging but have been used infrequently. We present here lifespan and lesion data from a study of mice bred as a cross between (AKR/J x DBA/2J)F, females and (C57BL/6J x SJL/J)F, males. In such a four-way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially available, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cause of illness in 42 of 44 animals. Malignant lymphoma, including at least four histopathologically distinct subtypes, was the most common cause and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a contributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerative lesions was also noted. The coefficient of variation for lifespan in these genetically heterogeneous mice was 26%, similar to that seen in analyses of recombinant inbred mouse lines. Baseline lifespan and pathology data on four-way cross mice is a useful prelude to the exploitation of this rodent model in tests of genetic and mechanistic hypotheses about aging.

show abstract

“…These mice are highly susceptible with the preweaning protocol but are resistant in terms of spontaneous tumors (54) and postweaning protocols (10,14,24). The biology and genetics of this unique susceptibility have been studied in detail (25,26 (10).…”

Section: Phenobarbital and 2-stage Hepatocarcinogenesismentioning

confidence: 99%

Review Article: Paradoxical Effects of Phenobarbital on Mouse Hepatocarcinogenesis

Lee¹

2000

Toxicol Pathol

View full text Add to dashboard Cite

Lifespan and Incidence of Cancer and Other Diseases in Selected Long-Lived Inbred Mice and Their F1 Hybrids2

Cited by 160 publications

References 0 publications

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

Lifespan and Lesions in Genetically Heterogeneous (Four-way Cross) Mice: A New Model for Aging Research

Review Article: Paradoxical Effects of Phenobarbital on Mouse Hepatocarcinogenesis

Contact Info

Product

Resources

About