Disease relevance of Aktip

• The most obvious phenotype of Ft/+ mice is a syndactyly of fore limbs characterised by a fusion of the tips of digits 1 to 4 [1].
• We have investigated the expression of left/right (L/R) asymmetry markers, nodal and lefty, in the situs inversus mouse mutant Fused toes (Ft) [2].
• The dominant mouse mutation Fused toes is characterized by partial syndactyly of the limbs and thymic hyperplasia [3].
• Two immature T cell lines (FT1 and FT4) were established after in vitro cloning of peripheral blood lymphocytes (PBLs) from an asymptomatic human immunodeficiency virus type 1 (HIV-1) seropositive, human T cell-lymphotropic virus type 1 seronegative homosexual subject [4].

High impact information on Aktip

• Programmed cell death is affected in the novel mouse mutant Fused toes (Ft) [5].
• In vivo we observed local ectopic expression of Id3 and Msx-2 mRNAs in Ft/+ embryos at overlapping regions of ectopic Bmp4 misexpression [6].
• The mouse mutant Ft displays thymic hyperplasia and fused toes (Ft) of the forelimbs [7].
• The rate of cell division and the cell turnover of immature CD4-8- and CD4+8+ thymocytes under steady state conditions are not altered in hyperplastic Ft thymi [7].
• Given the diversity, localisation and nature of the defects, we propose that some of them are caused by the elimination of the IrxB cluster, while others result from the loss of one or several of the Fts, Ftm and Fto genes [8].

Biological context of Aktip

• In addition, our analysis reveals a specific requirement of the genes deleted by the Ft mutation in hindlimb morphogenesis [9].
• In Ft mice a large chromosomal deletion (about 300 kb) occurred after insertional mutagenesis [3].
• Owing to this deletion, six genes, including the entire IroquoisB (IrxB) gene cluster, are directly affected by the Ft mutation [10].
• We established a physical as well as a gene map of the Ft locus, showing that the transgene integration resulted in a deletion of 1.6 Mb of genomic sequences on mouse Chromosome 8 [10].
• In wild type mice, Ft1 expression levels were found to be high in brain, kidney, and testes and detectable in all other adult organs and throughout embryonic development [3].

Anatomical context of Aktip

• These data support the idea that Ft genes play an important role in dorsal-ventral patterning of the neural tube acting to define the extent of motor neuron generation; moreover, the data reveal a previously unanticipated function for Ft genes in the maintenance of the floor plate [11].
• In Ft mutants starting from embryonic day 10.5, the floor plate appeared to degenerate and the notochord failed to undergo ventral displacement from the spinal cord [11].
• The tempospatial expression of genes involved in limb development revealed that patterning of Ft/+ limb buds is not affected by the mutation [1].
• As a result of transgenic insertional mutagenesis, heterozygous Fused toes (Ft) mice display a syndactyly of forelimbs and a thymic hyperplasia [10].
• Ft/Ft embryos die in midgestation showing severe malformations of fore- and midbrain as well as randomized situs [3].

Other interactions of Aktip

• Consistent with the loss of Shh signalling from the floor plate, V3 neuron generation was reduced in Ft/Ft embryos and the domain of motor neuron generation expanded ventrally at the expense of V2 neurons [11].
• We show that Ft affects all three axes as the mutant limbs display severe distal truncations of skeletal elements as well as an anteroposterior and an unusual form of dorsoventral polydactyly [9].
• Syndactyly of Ft/+ mice correlates with an imbalance in bmp4 and fgf8 expression [1].
• The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function in the establishment of handedness [2].
• Despite the close linkage, p130 expression appeared not to be affected by the Ft mutation [3].

References