Additionally, they highlight the limitations of single analysis methods. To acknowledge the proposed novel molecular mechanism of proIL-1beta in the early innate immune signaling during mastitis, additional studies are mandatory. Attractive options to extend our current findings are either the use of acute models with other relevant mastitic germs, or of more complex chronic mouse mastitis models and last but not least of different mammalian target species, especially dairy animals. Lymphoid nuclear protein related to AF4 is one of an estimated 40 genes that can form such MLL fusions, although LAF4 is one of the few genes that is aberrantly translocated in both B- and T-cell derived leukemia. Moreover, LAF4 has been found to be abnormally expressed in approximately 20 percent of breast cancers, suggesting that it may act as a proto-oncogene. A human microdeletion of 500 kb on chromosome 2q11.1 encompassing only the LAF4 gene has been detected by array comparative genomic MK-2206 2HCl Akt inhibitor hybridization on peripheral lymphocytes. The patient presented with developmental delay, seizures, urogenital and limb defects and died at four months of age after numerous repeated apnoeic episodes. The patient was also noted to be of low birth weight, and magnetic resonance imaging revealed a dilated ventricular system with cortical and subcortical brain atrophy. In addition, a recent study identified a CGG repeat expansion in the promoter of LAF4 at an autosomal folatesensitive fragile site named FRA2A that is associated with ID. It was shown that this polymorphic repeat is hypermethylated in FRA2A leading to silencing of LAF4 in the nervous system. However, the functional consequences of such a reduction in LAF4 expression are unknown. While a mouse Fmr2 null mutant does show some subtle behavioral and electrophysiological deficits related to synaptic plasticity, gene knockouts of Af4 and Af5q31 have not revealed a great deal regarding the normal molecular function of AFF proteins and no Laf4 mutants have been reported to date. Interestingly, a dominant point mutation in Af4 in the robotic ataxic mutant mouse reduces the turn-over of the protein by seven in absentia homolog proteins, a family of E3 ubiquitin-protein ligases; these data have revealed the importance of Af4 in the survival of Purkinje neurons in the cerebellum. AFF proteins were originally described as putative transcription factors based on the presence of a conserved transactivation domain. Importantly, subsequent biochemical studies demonstrated the key role that AFF proteins play in mediating transcriptional activity, revealing an association with the positive transcription elongation factor b. P-TEFb, AF4 and ENL/AF9 form a large complex capable of interacting with RNA polymerase II and this complex can also interact with disruptor of telomeric silencing to enhance methylation at histone 3 lysine residue 79. This complex has since become widely studied as a source of aberrant transcriptional activity related to oncogenesis in MLL/AFF protein fusion events and more recently in the direct transcriptional control of integrated HIV genomes.