Disease relevance of Nhlh2

• Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene [1].
• Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism [1].
• Targeted deletion of Nhlh2 (N2KO) in mice results in hypogonadism and obesity [2].
• To gain further insights into this process, we screened for NSCL target genes using DNA array hybridization and detected necdin, which is deleted in the human Prader-Willi syndrome phenotypically resembling the NSCL-2 mutation [3].
• HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma [4].

Psychiatry related information on Nhlh2

• These data demonstrate a role for the Nhlh2 transcription factor in controlling genes important to energy expenditure, and more specifically voluntary physical activity of animals [5].

High impact information on Nhlh2

• During murine embryogenesis, Nhlh1 and Nhlh2 share an overlapping but distinct pattern of expression in the developing nervous system [1].
• Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary [1].
• Male Nhlh2-/- mice are microphallic, hypogonadal and infertile with alterations in circulating gonadotropins, a defect in spermatogenesis and a loss of instinctual male sexual behaviour [1].
• Female Nhlh2-/- mice reared alone are hypogonadal, but when reared in the presence of males, their ovaries and uteri develop normally and they are fertile [1].
• NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression [3].

Chemical compound and disease context of Nhlh2

• Deletion of the Nhlh2 transcription factor decreases the levels of the anorexigenic peptides alpha melanocyte-stimulating hormone and thyrotropin-releasing hormone and implicates prohormone convertases I and II in obesity [6].

Biological context of Nhlh2

• Heterozygosity for the closely related transcription factor Nhlh2 increased the severity of the Nhlh1-null phenotype [7].
• The Nhlh2 transcription factor is required for female sexual behavior and reproductive longevity [2].
• The NSCL-2 gene maps to murine chromosome 3 [8].
• The temporally and tissue restricted pattern of expression of this gene and its identification as a member of a family of transcription factors relevant to growth and development in a wide variety of species suggest a role for NSCL-2 in the development of the eukaryotic nervous system [8].
• Both NSCL-1 and NSCL-2 genes are active only in postmitotic neurons, indicating a role for neuronal cell migration and/or differentiation within the sensory system [9].

Anatomical context of Nhlh2

• Using dual-label in situ hybridization, we demonstrate that, in the arcuate nucleus of the adult hypothalamus (ARC), Nhlh2 expression can be found in rostral proopiomelanocortin (POMC) neurons, whereas in the paraventricular nucleus (PVN), Nhlh2 is expressed in TRH neurons [6].
• HEN1 and HEN2 are coexpressed in the IMR-32 human neuroblastoma cell line, and they encode highly related proteins of 133 and 135 residues, respectively, that share 98% amino acid identity in their hHLH domains [4].
• The expression of NSCL-2 was restricted to developing cranial ganglia, the retina and the vestibular nerve [9].
• We further present a detailed expression analysis of NSCL-1 and NSCL-2 during sensory neuron development [9].
• We examined the expression of basic helix-loop-helix transcription factors NSCL1 and NSCL2 in the olfactory epithelium (OE) and the vomeronasal organ (VNO) during development [10].

Regulatory relationships of Nhlh2

• Nhlh-2 mRNA was coexpressed in a subpopulation (30%) of ARC neurons expressing pro-opiomelanocortin (POMC) mRNA, suggesting a potential functional relationship [11].
• In vitro assays indicated that Nhlh2 expression is regulated in parallel with GnRHR expression [12].

Other interactions of Nhlh2

• The nucleotide and predicted protein sequences of Nhlh1 and Nhlh2 are homologous within their bHLH domain where there are only three conservative amino acid differences [1].
• None of these regimes restored Nhlh-2 or NeuroD-1 to wild-type mRNA levels [11].

References