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Gene Review

Krit1  -  KRIT1, ankyrin repeat containing

Mus musculus

Synonyms: 2010007K12Rik, A630036P20Rik, AA432855, AI450393, AI643869, ...
 
 
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High impact information on Krit1

  • Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations [1].
  • In this study, we generated mice lacking Ccm1 and demonstrate that Ccm1 is ubiquitously expressed early in embryogenesis and is essential for vascular development [1].
  • Although the genetic evidence suggested somatic mutation of the wild-type Ccm1 allele, we were unable to demonstrate loss of heterozygosity by molecular methods [2].
  • In addition, we developed a real-time PCR strategy to accurately quantify the relative ratio of the two Krit1 alternative transcripts in different tissues, demonstrating a Krit1B/Krit1A ratio up to 20% in mouse thymus, but significantly lower ratios in other tissues [3].
  • Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1 [3].
 

Biological context of Krit1

  • Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons [4].
 

Anatomical context of Krit1

  • Unexpectedly, in vascular tissues, expression of Krit1 was detected only in large blood vessels of the embryo [5].
  • Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult [5].
  • These findings provide evidence of differential Krit1 and Rap1A expression during mouse ontogenesis and suggest a more widespread functional significance of Krit1, not restricted to vascular endothelial cells [6].
  • We show that the Krit1B splice isoform is widely expressed in mouse cell lines and tissues, whereas its expression is highly restricted in human [3].
 

Other interactions of Krit1

 

Analytical, diagnostic and therapeutic context of Krit1

  • The striking similarity of the human and mouse lesions indicates that the Ccm1(+/-) Trp53(-/-) mice are an appropriate animal model of CCM [2].

References

  1. Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Whitehead, K.J., Plummer, N.W., Adams, J.A., Marchuk, D.A., Li, D.Y. Development (2004) [Pubmed]
  2. Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations. Plummer, N.W., Gallione, C.J., Srinivasan, S., Zawistowski, J.S., Louis, D.N., Marchuk, D.A. Am. J. Pathol. (2004) [Pubmed]
  3. Identification of Krit1B: a novel alternative splicing isoform of cerebral cavernous malformation gene-1. Retta, S.F., Avolio, M., Francalanci, F., Procida, S., Balzac, F., Degani, S., Tarone, G., Silengo, L. Gene (2004) [Pubmed]
  4. Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons. Zhang, J., Clatterbuck, R.E., Rigamonti, D., Dietz, H.C. Genomics (2000) [Pubmed]
  5. Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in neurons and epithelial cells in embryo and adult. Denier, C., Gasc, J.M., Chapon, F., Domenga, V., Lescoat, C., Joutel, A., Tournier-Lasserve, E. Mech. Dev. (2002) [Pubmed]
  6. Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1). Kehrer-Sawatzki, H., Wilda, M., Braun, V.M., Richter, H.P., Hameister, H. Acta Neuropathol. (2002) [Pubmed]
  7. CCM2 expression parallels that of CCM1. Seker, A., Pricola, K.L., Guclu, B., Ozturk, A.K., Louvi, A., Gunel, M. Stroke (2006) [Pubmed]
 
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