An extensive phenotypic characterization of the hTNFalpha transgenic mice.
BACKGROUND
Tumor necrosis factor alpha (TNFalpha) is implicated in a wide variety of pathological and physiological processes, including chronic inflammatory conditions, coronary artery disease, diabetes, obesity, and cachexia. Transgenic mice expressing human TNFalpha (hTNFalpha) have previously been described as a model for progressive rheumatoid arthritis. In this report, we describe extensive characterization of an hTNFalpha transgenic mouse line.


RESULTS
In addition to arthritis, these hTNFalpha transgenic mice demonstrated major alterations in body composition, metabolic rate, leptin levels, response to a high-fat diet, bone mineral density and content, impaired fertility and male sexual function. Many phenotypes displayed an earlier onset and a higher degree of severity in males, pointing towards a significant degree of sexual dimorphism in response to deregulated expression of TNFalpha.


CONCLUSIONS
These results highlight the potential usefulness of this transgenic model as a resource for studying the progressive effects of constitutively expressed low levels of circulating TNFalpha, a condition mimicking that observed in a number of human pathological conditions.
Hayward
Michael D
MD
Caliper Discovery Alliances & Services (Xenogen Biosciences), 5 Cedar Brook Drive, Cranbury, NJ 08512, USA. Michael.Hayward@CaliperLS.com
Jones
Beverly K
BK
Saparov
Arman
A
Hain
Heather S
HS
Trillat
Anne-Cecile
AC
Bunzel
Michelle M
MM
Corona
Aaron
A
Li-Wang
Bifang
B
Strenkowski
Bryan
B
Giordano
Caroline
C
Shen
Hai
H
Arcamone
Emily
E
Weidlick
Jeffrey
J
Vilensky
Maria
M
Tugusheva
Marina
M
Felkner
Roland H
RH
Campbell
William
W
Rao
Yu
Y
Grass
David S
DS
Buiakova
Olesia
O
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha