Dwarf mouse

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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

  1. 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 @1@ 2Template: Webachiv / IABot / www.nia.nih.gov
  2. 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 @1@ 2Template: Webachiv / IABot / www.nia.nih.gov
  3. ^ 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).
  4. 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 .
  5. 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 .
  6. 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).
  7. 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.
  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
  9. 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

Web links