Abstract:
:The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a-->g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absence (sma1/sma1) of the GH-mediated peripubertal growth spurt, with sma1/+ mice displaying a less pronounced phenotype. All genotypes are viable and fertile, and the mode of inheritance is in accordance with a semidominant Mendelian trait. Adult SMA1 mice accumulate excessive amounts of sc and visceral fat in the presence of elevated plasma ghrelin levels, possibly reflecting altered energy partitioning. Our results suggest impaired storage and/or secretion of pituitary GH in mutants, resulting in reduced pituitary GH and reduced GH-stimulated IGF-1 expression. Generation and identification of the SMA1 mouse exemplifies the power of the combination of random mouse mutagenesis with a highly detailed phenotype-analysis as a successful strategy for the detection and analysis of novel gene-function relationships.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Meyer CW,Korthaus D,Jagla W,Cornali E,Grosse J,Fuchs H,Klingenspor M,Roemheld S,Tschöp M,Heldmaier G,De Angelis MH,Nehls Mdoi
10.1210/en.2003-1125subject
Has Abstractpub_date
2004-05-01 00:00:00pages
2531-41issue
5eissn
0013-7227issn
1945-7170pii
en.2003-1125journal_volume
145pub_type
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