Inactivation of tensin3 in mice results in growth retardation and postnatal lethality.
Tensin family is a group of focal adhesion proteins that interact with integrins, actin, and phosphotyrosine-containing proteins. To explore the in vivo functions of a new member of the family, tensin3, we have generated mutant mice with a disrupted tensin3 gene. Inactivation of tensin3 resulted in growth retardation and postnatal lethality in one third of the homozygous mutants. Histological analysis of those mutants showed incomplete development of the small intestine, lung, and bone. Villus formation in the small intestine was affected and cells migrated slower in the runt mutants. Their lungs also displayed enlarged air space suggesting defects in alveogenesis. In addition, the resting zone was thicker and fewer proliferating cells were present in the growth plates of tensin3(-/-) tibiae. These observations indicate that tensin3 is essential for normal development and functions of the small intestine, lung, and bone. These phenotypes of the runt tensin3(-/-) mice are similar to some clinical features of Silver-Russell syndrome (SRS) which is a genetically inherited defect. About 10% of SRS cases have been linked to abnormality in chromosome 7p11.2-13, where human tensin3 gene is located, suggesting a potential link between tensin3 and SRS.
Chiang
Ming-Ko
MK
Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, University of California-Davis, 4635 Second Avenue, Room 2000, Sacramento, CA 95817, USA.
Liao
Yi-Chun
YC
Kuwabara
Yasuko
Y
Lo
Su Hao
SH
D000015:Abnormalities, Multiple; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D008168:Lung / Q000002:abnormalities / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D000070876:Tensins; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000603370:TNS3 protein, human; D000070876:Tensins; D010749:Phosphoprotein Phosphatases; C500779:Tns3 protein, mouse