Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span

David S. Park, Alex W. Cohen, Philippe G. Frank, Babak Razani, Hyangkyu Lee, Terence M. Williams, Madhulika Chandra, Jamshid Shirani, Andrea P. De Souza, Baiyu Tang, Linda A. Jelicks, Stephen M. Factor, Louis M. Weiss, Herbert B. Tanowitz, Michael P. Lisanti

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Caveolae are 50-100 nm flask-shaped invaginations of the plasma membrane found in most cell types. Caveolin-1 is the principal protein component of caveolae membranes in nonmuscle cells. The recent development of Cav-1-deficient mice has allowed investigators to study the in vivo functional role of caveolae in the context of a whole animal model, as these mice lack morphologically detectable caveolae membrane domains. Surprisingly, Cav-1 null mice are both viable and fertile. However, it remains unknown whether loss of caveolin-1 significantly affects the overall life span of these animals. To quantitatively determine whether loss of Cav-1 gene expression confers any survival disadvantages with increasing age, we generated a large cohort of mice (n = 180), consisting of Cav-1 wild-type (+/+) (n = 53), Cav-1 heterozygous (+/-) (n = 70), and Cav-1 knockout (-/-) (n = 57) animals, and monitored their long-term survival over a 2 year period. Here, we show that Cav-1 null (-/-) mice exhibit an ∼50% reduction in life span, with major declines in viability occurring between 27 and 65 weeks of age. However, Cav-1 heterozygous (+/-) mice did not show any changes in long-term survival, indicating that loss of both Cav-1 alleles is required to mediate a reduction in life span. Mechanistically, these dramatic reductions in life span appear to be secondary to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy in Cav-1 null mice. Taken together, our results provide the first demonstration that loss of Cav-1 gene expression and caveolae organelles dramatically affects the long-term survival of an organism. In addition, aged Cav-1 null mice may provide a new animal model to study the pathogenesis and treatment of progressive hypertrophic cardiomyopathy and sudden cardiac death syndrome.

Original languageEnglish
Pages (from-to)15124-15131
Number of pages8
JournalBiochemistry
Volume42
Issue number51
DOIs
Publication statusPublished - 2003 Dec 30

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Caveolin 1
Animals
Caveolae
Gene expression
Membranes
Cell membranes
Demonstrations
Animal Models
Gene Expression
Pulmonary Fibrosis
Hypertrophic Cardiomyopathy
Sudden Cardiac Death
Cardiomegaly
Pulmonary Hypertension
Organelles
Proteins
Alleles
Research Personnel
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Park, D. S., Cohen, A. W., Frank, P. G., Razani, B., Lee, H., Williams, T. M., ... Lisanti, M. P. (2003). Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span. Biochemistry, 42(51), 15124-15131. https://doi.org/10.1021/bi0356348
Park, David S. ; Cohen, Alex W. ; Frank, Philippe G. ; Razani, Babak ; Lee, Hyangkyu ; Williams, Terence M. ; Chandra, Madhulika ; Shirani, Jamshid ; De Souza, Andrea P. ; Tang, Baiyu ; Jelicks, Linda A. ; Factor, Stephen M. ; Weiss, Louis M. ; Tanowitz, Herbert B. ; Lisanti, Michael P. / Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span. In: Biochemistry. 2003 ; Vol. 42, No. 51. pp. 15124-15131.
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abstract = "Caveolae are 50-100 nm flask-shaped invaginations of the plasma membrane found in most cell types. Caveolin-1 is the principal protein component of caveolae membranes in nonmuscle cells. The recent development of Cav-1-deficient mice has allowed investigators to study the in vivo functional role of caveolae in the context of a whole animal model, as these mice lack morphologically detectable caveolae membrane domains. Surprisingly, Cav-1 null mice are both viable and fertile. However, it remains unknown whether loss of caveolin-1 significantly affects the overall life span of these animals. To quantitatively determine whether loss of Cav-1 gene expression confers any survival disadvantages with increasing age, we generated a large cohort of mice (n = 180), consisting of Cav-1 wild-type (+/+) (n = 53), Cav-1 heterozygous (+/-) (n = 70), and Cav-1 knockout (-/-) (n = 57) animals, and monitored their long-term survival over a 2 year period. Here, we show that Cav-1 null (-/-) mice exhibit an ∼50{\%} reduction in life span, with major declines in viability occurring between 27 and 65 weeks of age. However, Cav-1 heterozygous (+/-) mice did not show any changes in long-term survival, indicating that loss of both Cav-1 alleles is required to mediate a reduction in life span. Mechanistically, these dramatic reductions in life span appear to be secondary to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy in Cav-1 null mice. Taken together, our results provide the first demonstration that loss of Cav-1 gene expression and caveolae organelles dramatically affects the long-term survival of an organism. In addition, aged Cav-1 null mice may provide a new animal model to study the pathogenesis and treatment of progressive hypertrophic cardiomyopathy and sudden cardiac death syndrome.",
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Park, DS, Cohen, AW, Frank, PG, Razani, B, Lee, H, Williams, TM, Chandra, M, Shirani, J, De Souza, AP, Tang, B, Jelicks, LA, Factor, SM, Weiss, LM, Tanowitz, HB & Lisanti, MP 2003, 'Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span', Biochemistry, vol. 42, no. 51, pp. 15124-15131. https://doi.org/10.1021/bi0356348

Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span. / Park, David S.; Cohen, Alex W.; Frank, Philippe G.; Razani, Babak; Lee, Hyangkyu; Williams, Terence M.; Chandra, Madhulika; Shirani, Jamshid; De Souza, Andrea P.; Tang, Baiyu; Jelicks, Linda A.; Factor, Stephen M.; Weiss, Louis M.; Tanowitz, Herbert B.; Lisanti, Michael P.

In: Biochemistry, Vol. 42, No. 51, 30.12.2003, p. 15124-15131.

Research output: Contribution to journalArticle

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AU - Park, David S.

AU - Cohen, Alex W.

AU - Frank, Philippe G.

AU - Razani, Babak

AU - Lee, Hyangkyu

AU - Williams, Terence M.

AU - Chandra, Madhulika

AU - Shirani, Jamshid

AU - De Souza, Andrea P.

AU - Tang, Baiyu

AU - Jelicks, Linda A.

AU - Factor, Stephen M.

AU - Weiss, Louis M.

AU - Tanowitz, Herbert B.

AU - Lisanti, Michael P.

PY - 2003/12/30

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Park DS, Cohen AW, Frank PG, Razani B, Lee H, Williams TM et al. Caveolin-1 Null (-/-) Mice Show Dramatic Reductions in Life Span. Biochemistry. 2003 Dec 30;42(51):15124-15131. https://doi.org/10.1021/bi0356348