Dwarf mouse
Dwarf mice ( English singular : dwarf mouse , dwarf = 'dwarf') are small mouse mutants and important model organisms in biogerontology .
Description and types
Dwarf mice are mutants of the Mus musculus species ( house mouse , or their cultivated form, color mouse , genus : mice) and should not be confused with the harvest mouse ( Micromys minutus ) from the Micromys genus .
Depending on the type of mutation, a distinction is made between Ames Dwarf mice and Snell Dwarf mice . The Ames Dwarf mice have a mutation in the Prop1 gene ( Prop1df ). Homozygous Ames Dwarf mice ( Prop1df / Prop1df ) are small and have a significantly higher life expectancy than their non-mutated conspecifics. In contrast, heterozygous Ames Dwarf mice ( Prop1df / +) are “normal”.
Snell Dwarf mice carry a recessive mutation on the Pit-1 gene. Here, too, the heterozygous animals are normal, while the homozygous animals only reach about a third of the body size and have a higher life expectancy.
The Laron Dwarf mouse is a relatively new mouse mutant that is obtained by specifically switching off (gene knockout) the growth hormone receptor. These animals are therefore also referred to as GHR-KO mice . The name Laron is dedicated to the Israeli endocrinologist Zvi Laron (* 1927), who is also the godfather of Laron's syndrome (pituitary short stature caused by somatotropin resistance).
Ames Dwarf mice display many phenotypic characteristics that animals under calorie restriction also display. However, the higher life expectancy of the dwarf mice is caused by other phenomena and mechanisms. One indication of this is that calorie restriction in dwarf mice further increases life expectancy. The comparison of the gene expression of dwarf mice with that of normal mice under calorie restriction (30% reduction in diet) showed significant differences. In contrast to the two other Dwarf mouse mutants and other mice, the calorie restriction in the Laron Dwarf mice has no life-prolonging effect.
In the first two weeks after their birth, the Dwarf mice do not differ in growth from their heterozygous littermates. The females of the Ames and Snell mice are sterile. The males have low fertility . The life span is increased by 68% in females and by 49% in males. The body weight is 67% less than that of the wild type. In both mutants, no somatotropin (growth hormone, GH), no thyrotropin (TSH) and no prolactin (PRL) is produced. There are lower glucose and insulin levels in the plasma . IGF-1 is reduced by over 99%.
The mechanisms that lead to a life extension in dwarf mice are still largely not understood. For example, if Snell-Dwarf mice are injected with growth hormone and thyroxine , their body weight increases as expected; by about 45%. However, they remain significantly smaller than the heterozygous specimens. The fertility of the males is normalized again through the administration of growth hormones. However, this measure does not reduce life expectancy. Life expectancy was reduced by the thyroxine, but it was still higher than that of the comparison animals.
Individual evidence
- ↑ National Institute on Aging: Mouse Models: Ames Dwarf Mouse (Taconic Line 000324). ( Memento of the original from December 20, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved January 8, 2011
- ↑ National Institute on Aging: Mouse Models: Snell Dwarf Mouse (Taconic Line 3623). ( Memento of the original from December 20, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Retrieved January 8, 2011
- ^ Z. Laron: Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity? In: Mechanisms of aging and development Volume 126, Number 2, February 2005, pp. 305-307, ISSN 0047-6374 . doi : 10.1016 / j.mad.2004.08.022 . PMID 15621211 . (Review).
- ↑ Z. Laron, A. Pertzelan, S. Mannheimer: Genetic pituitary dwarfism with high serum concentration of growth hormone-a new inborn error of metabolism? In: Israel journal of medical sciences Volume 2, Number 2, 1966 Mar-Apr, pp. 152-155, ISSN 0021-2180 . PMID 5916640 .
- ↑ MM Masternak, K. Al-Regaiey, MS Bonkowski, J. Panici, L. Sun, J. Wang, GK Przybylski, A. Bartke: Divergent effects of caloric restriction on gene expression in normal and long-lived mice. In: The journals of gerontology. Series A, Biological sciences and medical sciences Volume 59, Number 8, August 2004, pp. 784-788, ISSN 1079-5006 . PMID 15345726 .
- ↑ O. Arum, MS Bonkowski, JS Rocha, A. Bartke: The growth hormone receptor gene-disrupted mouse fails to respond to an intermittent fasting diet. In: Aging cell Volume 8, Number 6, December 2009, pp. 756-760, ISSN 1474-9726 . doi : 10.1111 / j.1474-9726.2009.00520.x . PMID 19747233 . PMC 2783987 (free full text).
- ↑ H. Breitsameter: Holistic proteome analysis of the adrenal gland bGH and IGFBP-2 transgenic mice. (PDF file; 4.10 MB) Dissertation, LMU Munich, 2007, p. 8.
- ↑ CE Finch: The Biology of Human Longevity: Inflammation, Nutrition, and Aging in the Evolution of Lifespans. Academic Press, 2007, ISBN 0-123-73657-9 limited preview in Google Book Search
- ↑ M. Vergara et al .: Hormone-treated snell dwarf mice regain fertility but remain long lived and disease resistant. In: J Gerontol A Biol Sci Med Sci 59, 2004, pp. 1244-1250. PMID 15699523
further reading
- YF Chen, CY Wu, CH Kao, TF Tsai: Longevity and lifespan control in mammals: lessons from the mouse. In: Aging research reviews Volume 9 Suppl 1, November 2010, pp. S28-S35, ISSN 1872-9649 . doi : 10.1016 / j.arr.2010.07.003 . PMID 20667513 .
- HM Brown-Borg et al: Growth Hormone and Aging in Mice. In: C. Sell and A. Lorenzini: Life Span Extension: Single Cell Organisms to Man. Humana Press, 2009, ISBN 1-603-27506-1 , pp. 115-131. limited preview in Google Book search
- WR Swindell: Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse. In: BMC genomics Volume 10, 2009, p. 585, ISSN 1471-2164 . doi : 10.1186 / 1471-2164-10-585 . PMID 19968875 . PMC 2795771 (free full text). ( Open access )
- WR Swindell: Gene expression profiling of long-lived dwarf mice: longevity-associated genes and relationships with diet, gender and aging. In: BMC genomics Volume 8, 2007, p. 353, ISSN 1471-2164 . doi : 10.1186 / 1471-2164-8-353 . PMID 17915019 . PMC 2094713 (free full text). ( Open access )
- JJ McElwee, E. Schuster, E. Blanc, MD Piper, JH Thomas, DS Patel, C. Selman, DJ Withers, JM Thornton, L. Partridge, D. Gems: Evolutionary conservation of regulated longevity assurance mechanisms. In: Genome biology Volume 8, Number 7, 2007, p. R132, ISSN 1465-6914 . doi : 10.1186 / gb-2007-8-7-r132 . PMID 17612391 . PMC 2323215 (free full text). ( Open access )
- A. Bartke: Life Extension in the Dwarf Mouse. In: Handbook of Models for Human Aging. PM Conn (editor), Academic Press, 2006, ISBN 0-123-69391-8 , pp. 403-413, limited preview in Google Book Search
- A. Bartke and H. Brown-Borg: Life extension in the dwarf mouse. In: Curr Top Dev Biol 63, 2004, pp. 189-225. PMID 15536017 (Review)
- H. Liang, EJ Masoro, JF Nelson, R. Strong, CA McMahan, A. Richardson: Genetic mouse models of extended lifespan. In: Experimental Gerontology Volume 38, Numbers 11-12, 2003 Nov-Dec, pp 1353-1364, ISSN 0531-5565 . PMID 14698816 . (Review).
- A. Bartke, JC Wright, JA Mattison, DK Ingram, RA Miller, GS Roth: Extending the lifespan of long-lived mice. In: Nature Volume 414, Number 6862, November 2001, p. 412, ISSN 0028-0836 . doi : 10.1038 / 35106646 . PMID 11719795 .
- K. Flurkey, J. Papaconstantinou, RA Miller, DE Harrison: Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. In: Proceedings of the National Academy of Sciences Volume 98, Number 12, June 2001, pp. 6736-6741, ISSN 0027-8424 . doi : 10.1073 / pnas.111158898 . PMID 11371619 . PMC 34422 (free full text).
- L. Guarente: Mutant mice live longer. In: Nature 402, 1999, pp. 243-245. doi : 10.1038 / 46185 PMID 10580490
- HM Brown-Borg, KE Borg, CJ Meliska, A. Bartke: Dwarf mice and the aging process. In: Nature Volume 384, Number 6604, November 1996, p. 33, ISSN 0028-0836 . doi : 10.1038 / 384033a0 . PMID 8900272 .
- RR Behringer et al .: Dwarf mice produced by genetic ablation of growth hormone-expressing cells. In: Genes Dev 2, 1988, pp. 453-461. PMID 3286373