Disruption of the Csk gene, encoding a negative regulator of Src family tyrosine kinases, leads to neural tube defects and embryonic lethality in mice

Article Abstract:

Mutations are caused when several members of the Src family are activated by a mice mutant for C-Src kinase (csk), which is a novel kinase that phosphorylates several Src family kinase at the carboxy-terminal tyrosine. The tyrosine is a major regulatory site for kinase activity, and leads to a recessive lethal phenotype at midgestation, which includes defects in the notochord and in the neural tube during the early embryonic development in mice. The notochord is a transient structure of mesodermal origin, and is localized between the floor plates of the neural tube.

author: Soriano, Philippe, Akira Imamoto
Animal mutation

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Constitutive activation of Src family kinases in mouse embryos that lack Csk

Article Abstract:

C-Src kinase (csk), a cytoplasmic protein-tyrosine kinase, inhibits the kinase activity of Src family members by phosphorylating the negative regulatory tyrosine residue of Src. Csk-deficient embryos of mice exhibit characteristic abnormality in the development of neural tissues when the expression of p60 (super c-src) increases. An elevation in the kinase activity of p60 (super c-src) in csk-deficient embryos is due to a substantial reduction of phosphate on Tyr-527. Csk acts as anti-oncogene through its negative regulation of Src family kinases.

author: Shigeyuki Nada, Takeshi Yagi, Hiroyuki Takeda, Tomoyuki Tokunaga, Hachiro Nakagawa, Yoji Ikawa, Masato Okada, Shinichi Aizawa
Influence, Protein tyrosine kinase, Protein-tyrosine kinase

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Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes

Article Abstract:

Mutant mice homozygous for the gene encoding Huntington's disease (HD) died before reaching embryonic day 8.5. However, the mice reached the initial stages of gastrulation, but failed to reach organogenesis. On the other hand, heterozygous mice exhibited increased motor activity and cognitive deficits associated with neuronal loss in the subthalamic nucleus. These results suggest that the HD gene plays a role in the normal development of the basal ganglia.

author: Marth, Jamey D., Hayden, Michael R., Nasir, Jamal, Floresco, Stan B., O'Kusky, John R., Diewert, Virginia M., Richman, Joy M., Zeisler, Jutta, Borowski, Anita, Phillips, Anthony G.
Genetic aspects, Mice, Mice (Rodents), Huntington's chorea, Huntington's disease, Basal ganglia

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subjects list: Research, Abnormalities, Neural tube, Neural tube defects
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