- Email: [email protected]
Insights into implantation
540
News & Comment
with isolated CLP than unaffected controls (0.4%). Despite this very significant result, W185X is only a moderate risk factor for CLP, as the majority of patients with CLP did not carry this mutation. The remainder of the PVRL1 gene was not examined, so the possibility that other mutations in this gene might also predispose to isolated CLP should be a priority area of research.
TRENDS in Molecular Medicine Vol.7 No.12 December 2001
In addition, of course, TBX22 is now also a candidate gene. Increasing knowledge of how these and other genes contribute to human CLP, together with good animal models of cleft palate, should ultimately lead to a better understanding of which environmental factors are important and how they might be modulated to reduce overall risk.
1 Braybrook, C. et al. (2001) The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia. Nat. Genet. 29, 179–183 2 Sözen, M.A. et al. (2001) Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nat. Genet. 29, 141–142
Micheala A. Aldred [email protected]
In Brief
Lasker lads This year’s Lasker Basic Medical Research Award was given to three scientists who pioneered the development of gene targeting technologies in mice. The ability to ‘knock-out’ a chosen gene has led to the creation of numerous animal models for human genetic diseases. Martin Evans (Cardiff University, UK), Mario Capecchi (University of Utah) and Oliver Smithies (University of North Carolina, Chapel Hill, NC) were honored for their key contributions to the birth of the first knockout mice in 1989. Evans developed techniques to culture embryonic stem (ES) cells from mouse blastocysts. Capecchi and Smithies both figured out how to use homologous recombination to genetically modify the mouse genome. The 2001 Lasker Clinical Medical Research Award went to Robert Edwards (Cambridge University, UK) for the development of in vitro fertilization (IVF) technology. Together with Patrick Steptoe, Edwards overcame the technical challenges associated with isolating and manipulating human eggs. Their work led to the birth of the first ‘test-tube baby’ in 1978 and brought hope to millions of infertile couples. The Lasker Awards jury described these two technological advances as ‘revolutionary’. Winners of the prestigious Lasker awards have often gone on to be awarded the Nobel Prize. JW
Insights into implantation About 6% of people carry the Factor-V Leiden (FVL) mutation that is associated with increased deep-vein thrombosis, miscarriages and premature birth. Now, Wolfgang Gopel and colleagues (Lubeck University, Germany) have shown that there might be advantages to having the FVL mutation, which might explain why it has survived selection pressures during human evolution. They examined data from
http://tmm.trends.com
102 women who had had fertility treatment (intracytoplasmic sperm injection) and found that 90% of FVL cases resulted in successful implantation of fertilized eggs, compared with 49% in non-FVL mothers. These results, published in October in The Lancet, suggest that blood clotting might affect the implantation process and might lead to improved fertility treatments. JW
A pig with a luminous nose
developed a new mouse model of astrocytoma, the most prevalent and deadly of human brain tumours. These cancers originate from the glial populations of the brain and can proliferate aggressively, resulting in poor patient prognosis. By overexpressing the signalling protein Ras in the astrocytes of mice, a disease state remarkably similar to human astrocytoma was generated. Furthermore, by additionally enhancing production of epidermal growth factor receptor (EGF-R) by transgenesis in the same animals, the type of tumour produced was found to be much more aggressive. The results, presented during September’ annual meeting of the American Neurological Association in Chicago, strongly implicate the EGF signalling pathway in the formation of astrocytomas, and will provide a valuable tool for therapeutic testing. PoN
Photo courtesy of MU Extension and Agricultural Information
Transplanting brain cells
A litter of transgenic piglets, genetically modified to contain a functional copy of a fluorescent gene found in jellyfish, has been successfully generated by researchers from the University of Missouri, Columbia. The animals all have bright yellow noses and hooves, shown above, a visual indication of successful gene expression. One of the major obstacles to successful transplantation of pig organs to human donors is the likelihood of rejection. It is believed that generation of transgenic pigs would allow specific immune responses to be overcome. The production of these yellow-nosed piglets, published in Animal Biotechnology, is an important demonstration that the technology can work. PoN
Improvements in cell transplantation procedures are required if such technology is to be used to restore function in degenerative neurological disorders such as Parkinson’s and Huntington’s diseases, according to a report in Nature Biotechnology in October. Melissa Mahoney and Mark Saltzman (Cornell University, Ithaca, NY) have developed a technique for transplanting brain cells that attempts to maintain a cellular microenvironment that helps cell growth and differentiation. The technique is based on the creation of transplantable ‘neo-tissues’ formed by combining cells with controlledrelease polymeric particles in vitro. To test the system, they looked at the effect of local supply of nerve growth factor (NGF) on neo-tissues containing cholinergic neurons. They could demonstrate that the synthetic microenvironment could be controlled by changing the number of microparticles or the rate of NGF release. JW
Mouse model for astrocytoma Researchers based at the Washington University School of Medicine have
1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
with isolated CLP than unaffected controls (0.4%). Despite this very significant result, W185X is only a moderate risk factor for CLP, as the majority of patients with CLP did not carry this mutation. The remainder of the PVRL1 gene was not examined, so the possibility that other mutations in this gene might also predispose to isolated CLP should be a priority area of research.
TRENDS in Molecular Medicine Vol.7 No.12 December 2001
In addition, of course, TBX22 is now also a candidate gene. Increasing knowledge of how these and other genes contribute to human CLP, together with good animal models of cleft palate, should ultimately lead to a better understanding of which environmental factors are important and how they might be modulated to reduce overall risk.
1 Braybrook, C. et al. (2001) The T-box transcription factor gene TBX22 is mutated in X-linked cleft palate and ankyloglossia. Nat. Genet. 29, 179–183 2 Sözen, M.A. et al. (2001) Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nat. Genet. 29, 141–142
Micheala A. Aldred [email protected]
In Brief
Lasker lads This year’s Lasker Basic Medical Research Award was given to three scientists who pioneered the development of gene targeting technologies in mice. The ability to ‘knock-out’ a chosen gene has led to the creation of numerous animal models for human genetic diseases. Martin Evans (Cardiff University, UK), Mario Capecchi (University of Utah) and Oliver Smithies (University of North Carolina, Chapel Hill, NC) were honored for their key contributions to the birth of the first knockout mice in 1989. Evans developed techniques to culture embryonic stem (ES) cells from mouse blastocysts. Capecchi and Smithies both figured out how to use homologous recombination to genetically modify the mouse genome. The 2001 Lasker Clinical Medical Research Award went to Robert Edwards (Cambridge University, UK) for the development of in vitro fertilization (IVF) technology. Together with Patrick Steptoe, Edwards overcame the technical challenges associated with isolating and manipulating human eggs. Their work led to the birth of the first ‘test-tube baby’ in 1978 and brought hope to millions of infertile couples. The Lasker Awards jury described these two technological advances as ‘revolutionary’. Winners of the prestigious Lasker awards have often gone on to be awarded the Nobel Prize. JW
Insights into implantation About 6% of people carry the Factor-V Leiden (FVL) mutation that is associated with increased deep-vein thrombosis, miscarriages and premature birth. Now, Wolfgang Gopel and colleagues (Lubeck University, Germany) have shown that there might be advantages to having the FVL mutation, which might explain why it has survived selection pressures during human evolution. They examined data from
http://tmm.trends.com
102 women who had had fertility treatment (intracytoplasmic sperm injection) and found that 90% of FVL cases resulted in successful implantation of fertilized eggs, compared with 49% in non-FVL mothers. These results, published in October in The Lancet, suggest that blood clotting might affect the implantation process and might lead to improved fertility treatments. JW
A pig with a luminous nose
developed a new mouse model of astrocytoma, the most prevalent and deadly of human brain tumours. These cancers originate from the glial populations of the brain and can proliferate aggressively, resulting in poor patient prognosis. By overexpressing the signalling protein Ras in the astrocytes of mice, a disease state remarkably similar to human astrocytoma was generated. Furthermore, by additionally enhancing production of epidermal growth factor receptor (EGF-R) by transgenesis in the same animals, the type of tumour produced was found to be much more aggressive. The results, presented during September’ annual meeting of the American Neurological Association in Chicago, strongly implicate the EGF signalling pathway in the formation of astrocytomas, and will provide a valuable tool for therapeutic testing. PoN
Photo courtesy of MU Extension and Agricultural Information
Transplanting brain cells
A litter of transgenic piglets, genetically modified to contain a functional copy of a fluorescent gene found in jellyfish, has been successfully generated by researchers from the University of Missouri, Columbia. The animals all have bright yellow noses and hooves, shown above, a visual indication of successful gene expression. One of the major obstacles to successful transplantation of pig organs to human donors is the likelihood of rejection. It is believed that generation of transgenic pigs would allow specific immune responses to be overcome. The production of these yellow-nosed piglets, published in Animal Biotechnology, is an important demonstration that the technology can work. PoN
Improvements in cell transplantation procedures are required if such technology is to be used to restore function in degenerative neurological disorders such as Parkinson’s and Huntington’s diseases, according to a report in Nature Biotechnology in October. Melissa Mahoney and Mark Saltzman (Cornell University, Ithaca, NY) have developed a technique for transplanting brain cells that attempts to maintain a cellular microenvironment that helps cell growth and differentiation. The technique is based on the creation of transplantable ‘neo-tissues’ formed by combining cells with controlledrelease polymeric particles in vitro. To test the system, they looked at the effect of local supply of nerve growth factor (NGF) on neo-tissues containing cholinergic neurons. They could demonstrate that the synthetic microenvironment could be controlled by changing the number of microparticles or the rate of NGF release. JW
Mouse model for astrocytoma Researchers based at the Washington University School of Medicine have
1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.