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Gene Review

Nhlh2  -  nescient helix loop helix 2

Mus musculus

Synonyms: 6230401I09Rik, HEN-2, Helix-loop-helix protein 2, Hen2, NSCL-2, ...
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Disease relevance of Nhlh2


Psychiatry related information on Nhlh2


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


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


Regulatory relationships of Nhlh2


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].


  1. Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Good, D.J., Porter, F.D., Mahon, K.A., Parlow, A.F., Westphal, H., Kirsch, I.R. Nat. Genet. (1997) [Pubmed]
  2. The Nhlh2 transcription factor is required for female sexual behavior and reproductive longevity. Johnson, S.A., Marín-Bivens, C.L., Miele, M., Coyle, C.A., Fissore, R., Good, D.J. Hormones and behavior. (2004) [Pubmed]
  3. NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression. Krüger, M., Ruschke, K., Braun, T. EMBO J. (2004) [Pubmed]
  4. HEN1 and HEN2: a subgroup of basic helix-loop-helix genes that are coexpressed in a human neuroblastoma. Brown, L., Espinosa, R., Le Beau, M.M., Siciliano, M.J., Baer, R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  5. Reduced voluntary activity precedes adult-onset obesity in Nhlh2 knockout mice. Coyle, C.A., Jing, E., Hosmer, T., Powers, J.B., Wade, G., Good, D.J. Physiol. Behav. (2002) [Pubmed]
  6. 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. Jing, E., Nillni, E.A., Sanchez, V.C., Stuart, R.C., Good, D.J. Endocrinology (2004) [Pubmed]
  7. Predisposition to arrhythmia and autonomic dysfunction in Nhlh1-deficient mice. Cogliati, T., Good, D.J., Haigney, M., Delgado-Romero, P., Eckhaus, M.A., Koch, W.J., Kirsch, I.R. Mol. Cell. Biol. (2002) [Pubmed]
  8. NSCL-2: a basic domain helix-loop-helix gene expressed in early neurogenesis. Göbel, V., Lipkowitz, S., Kozak, C.A., Kirsch, I.R. Cell Growth Differ. (1992) [Pubmed]
  9. Functional redundancy of NSCL-1 and NeuroD during development of the petrosal and vestibulocochlear ganglia. Kr??ger, M., Schmid, T., Kr??ger, S., Bober, E., Braun, T. Eur. J. Neurosci. (2006) [Pubmed]
  10. Expression of bHLH transcription factors NSCL1 and NSCL2 in the mouse olfactory system. Suzuki, Y., Tsuruga, E., Yajima, T., Takeda, M. Chem. Senses (2003) [Pubmed]
  11. Hypothalamic bHLH transcription factors are novel candidates in the regulation of energy balance. Nilaweera, K.N., Ellis, C., Barrett, P., Mercer, J.G., Morgan, P.J. Eur. J. Neurosci. (2002) [Pubmed]
  12. Pubertal impairment in Nhlh2 null mice is associated with hypothalamic and pituitary deficiencies. Cogliati, T., Delgado-Romero, P., Norwitz, E.R., Guduric-Fuchs, J., Kaiser, U.B., Wray, S., Kirsch, I.R. Mol. Endocrinol. (2007) [Pubmed]
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