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

• METHODS: We analyzed the mRNA expression of Ccm1 and Ccm2 in the embryonic and postnatal mouse brain by in situ hybridization [7].

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