IGF Acid-labile Subunit Research Articles

Studies on the Indian catfish Clarias magur reveal Insulin‐Like Growth Factor II to be the major type and its upregulation in high‐growth performing fish

Expression of three growth-associated genes, IGF-I, IGF-II and IGF acid-labile subunit (IGFALS), was compared between highest and lowest growth performing families of Clarias magur being genetically selected for growth. Only IGF-II and IGFALS showed 3.50- and 2.10-fold differential expression, respectively, in RNASeq data of five pooled tissues, brain, liver, muscle, kidney and gonads. Relative expression profiling in brain, liver and muscle by qPCR showed 3.4-fold and 2.8-fold upregulation of IGF-II in muscle and liver, respectively, in higher performing family compared with the lower ones, while IGF-I was invariant and also the less expressed gene in all tissues. IGFALS expression was found to vary in accordance with IGF-II. Genotyping of one non-synonymous SNP (valine to isoleucine) identified in IGFALS revealed a significantly higher frequency of the isoleucine genotype in the high-performing group. Present study shows that in magur, IGF-Is significantly expressed not only in the liver but also in the muscle. Unlike other teleosts like cyprinids and cichlids where IGF-I has been reported to be the major component in the somatotropic axis, IGF-II is seen to be the major type in catfish, as also reported in Channel catfish, and is upregulated in high-growth individuals.

Constitutional delay of growth and puberty is not commonly associated with mutations in the acid labile subunit gene.

Constitutional delay of growth and puberty (CDGP) is a common clinical condition that may be inherited as an autosomal dominant, recessive or X-linked trait. However, single-gene defects underlying CDGP have not yet been identified. A small number of children (to date 10) with modest growth failure and in the majority delayed puberty, a phenotype similar to that of CDGP, have been reported to carry mutations in the IGF acid labile subunit (IGFALS) gene which encodes the ALS, a part of the ternary complex carrying IGF-I in the circulation. The aim of our study was to screen a well-characterised CDGP cohort exhibiting a range of growth retardation and pubertal delay for pathogenic sequence variants in IGFALS. We used denaturing high performance liquid chromatography (dHPLC) to screen for IGFALS mutations in DNA samples from 90 children (80 males) with CDGP of predominantly White European origin. DNA fragments generating abnormal waveforms were directly sequenced. No IGFALS mutation was identified in the coding sequences or exon-intron boundaries in our CDGP cohort. One abnormal waveform pattern in dHPLC in 15 children with CDGP was found to represent a recognised synonymous single-nucleotide polymorphism of the coding transcript in the second exon in residue 210 of IGFALS. IGFALS sequence variants are unlikely to be a common association with pubertal delay in children with CDGP.