Sci. Aging Knowl. Environ., 17 October 2001
Vol. 2001, Issue 3, p. tg13
GENETICALLY ALTERED MICE
||Snell Dwarf (Pit-1dw)
||Longevity data done on F1 (C3H/HeJ crossed with DW/J)
||Pit-1 (Pituitary-specific transcription factor 1)
|Type of change
||Two noncomplementing point mutations, Pit-1dwj and Pit-1dw
|Nature of protein
||A 291-amino acid, soluble protein, a transcription factor involved in the embryonic development of the pituitary gland.
||Small body size, stunted growth, obesity in late life. Females and males are usually sterile.
|Corresponding human phenotype
||Combined pituitary hormone deficiency
Online Mendelian Inheritance in Man (OMIM) entry for human PIT1: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173110
||F. Flurkey, J. Papaconstantinou, R. A. Miller, D. E. Harrison, Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. U.S.A. 98, 6736-6741 (2001).
||Two different strains of Snell Dwarf mice are available from the Jackson Laboratory (Stock numbers 000772 and 000942) (http://jaxmice.jax.org/).
||For more information on Snell dwarf mice, see below.
||OMIM entry for human PIT1:
Related transgenic/knockout mice:
Ames Dwarf Mice: http://sageke.sciencemag.org/cgi/content/full/sageke;2001/1/tg11
Little Mice: http://sageke.sciencemag.org/cgi/content/full/sageke;2001/4/tg14
SAGE KE's Genes/Interventions database:
||Growth hormone, life-span, Snell dwarf, Ames dwarf, pit-1, IGF-1.
Snell Dwarf Mice
The Snell dwarf mice are phenotypically very similar to the Ames mice. Both have a small adult body size and show increased longevity. The mutation causing the Snell phenotype is found in the Pit-1 gene (Pituitary-specific transcription factor 1), which is expressed in the pituitary gland during development. The Pit-1 and Prop-1 (Prophet of Pit-1) genes are expressed in the same cells during development but are expressed at different times. The Prop-1 gene is expressed 1 day earlier than the Pit-1 gene, and it is believed that these transcription factors act in the same molecular pathway--the one that controls the development of a subset of pituitary cells responsible for secreting growth hormone (GH), thyroid-stimulating hormone, and prolactin. As a result, both the Ames and Snell dwarf mice have very similar endocrine profiles.
At this time, it is not fully understood why Snell and Ames dwarf mice show increased longevity. Mutations in genes that encode insulin-like growth factor-1 (IGF-1) homologs in invertebrate model organisms have been shown to increase longevity. Therefore, it has been argued that the GH/IGF-1 hormonal axis may regulate longevity in invertebrates as well as in mammals. It is likely that the life-span extension observed in Snell and Ames dwarf mice occurs by the same mechanism. Snell mice have been reported to have a decreased metabolic rate, which perhaps explains their increased longevity.
October 17, 2001
A. Bartke, H. Brown-Borg, J. Mattison, B. Kinney, S. Hauck, C. Wright, Prolonged longevity of hypopituitary dwarf mice. Exp. Gerontol. 36, 21-28 (2001).[CrossRef][Medline]
A. Bartke, H. Brown-Borg, B. Kinney, J. Mattison, C. Wright, S. Hauck, K. Coschigano, J. J. Kopchick, Growth hormone and aging. J. Am. Aging Assoc. 23, 219-225 (2000).
K. Flurkey, J. Papaconstantinou, R. A. Miller, D. E. Harrison, Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. U.S.A. 98, 6736-6741 (2001).[Abstract/Free Full Text]
R. A. Miller, Kleemeier award lecture: are there genes for aging? J. Gerontol. A Biol. Sci. Med. Sci. 54, B297-B307 (1999).[Medline]