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The tenascin-C knockout revisited
1School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
Abstract:
In the past seven years, two groups have independently produced tenascin-C-knockout mice. These mice are born alive and, originally, were described as showing no abnormalities. More recent studies, many involving pathological intervention, have shown that tenascin-C-knockout mice have several defects. The mice exhibit abnormal behaviour, as well as abnormalities in brain chemistry. They also show defects in structure and repair of neuromuscular junctions, in the ability to recover from snake-venom-induced glomerulonephritis and in chemically induced dermatitis. Healing of skin wounds is morphologically normal, but the mice exhibit defects in healing after suture injury of corneas. In both skin and corneal wounds, fibronectin expression is abnormally low in tenascin-C-knockout mice. Finally, in vitro studies indicate that haemopoietic activity is defective in bone marrow from these mice. When examined together, these studies provide evidence for precise functions for tenascin-C, as well as an explanation for why the sequence of tenascin-C is so highly phylogenetically conserved.
Insights
Tenascin-C knockout mice reveal critical roles for this protein in neurological, immune, and tissue repair functions. These findings explain tenascin-C
Area of Science:
- Extracellular matrix biology
- Molecular genetics
- Developmental biology
Background:
- Tenascin-C is an extracellular matrix glycoprotein implicated in various biological processes.
- Previous studies suggested tenascin-C knockout mice lacked observable abnormalities.
- Recent research indicates potential roles for tenascin-C in physiological and pathological contexts.
Purpose of the Study:
- To investigate the precise functions of tenascin-C using knockout mouse models.
- To elucidate the physiological and pathological consequences of tenascin-C deficiency.
- To understand the evolutionary significance of tenascin-C's conserved sequence.
Main Methods:
- Generation and analysis of tenascin-C-knockout mice.
- Behavioral and biochemical assessments of knockout mice.
- Pathological interventions including snake venom and chemical induction.
- Histological examination of tissue repair (skin, cornea, neuromuscular junctions).
- In vitro studies of bone marrow hematopoietic activity.
Main Results:
- Tenascin-C knockout mice exhibit abnormal behavior and brain chemistry.
- Defects observed in neuromuscular junction structure/repair, glomerulonephritis recovery, and dermatitis.
- Impaired corneal wound healing and reduced fibronectin expression in both skin and corneal wounds.
- Defective hematopoietic activity in bone marrow from knockout mice.
Conclusions:
- Tenascin-C plays crucial roles in neurological function, immune response, and tissue repair.
- The diverse defects in knockout mice highlight tenascin-C's importance in multiple physiological systems.
- These findings provide a functional basis for the high phylogenetic conservation of tenascin-C.