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Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene

Nature Genetics volume 15, pages 397–401 (1997)Cite this article

Abstract

The family of basic helix-loop-helix (bHLH) genes comprises transcription factors involved in many aspects of growth and development. We have previously described two bHLH transcription factors, Nhlh1 and Nhlh2 (originally named NSCL1 and NSCL2)1–3. The nucleotide and predicted protein sequences of Nhlh1 and Nhlh2 are homologous within their bHLH domain where there are only three conservative amino acid differences2,3. During murine embryogenesis, Nhlh1 and Nhlh2 share an overlapping but distinct pattern of expression in the developing nervous system1,2. To improve our understanding of the role of these genes during neurogenesis, we have generated mice containing targeted deletions of both genes and here describe our results for Nhlh2. Loss of Nhlh2 results in a disruption of the hypothalamic-pituitary axis in mice. 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. 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. Both male and female homozygotes exhibit progressive adult-onset obesity. Nhlh2 is expressed in the ventral-medial and lateral hypothalamus, Rathke's pouch and in the anterior lobe of the adult pituitary. Our results support a role for Nhlh2 in the onset of puberty and the regulation of body weight metabolism.

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Author notes

  1. Ilan R. Kirsch: Correspondence should be addressed to I.R.K.

Authors and Affiliations

  1. Acquired Gene Rearrangement Section, National Cancer Institute, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20889, USA

    Deborah J. Good & Ilan R. Kirsch

  2. Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20889, USA

    Forbes D. Porter, Kathleen A. Mahon & Heiner Westphal

  3. Pituitary Hormones and Antisera Center, Harbor-UCLA Medical Center, Torrance, California, 90509, USA

    Albert F Parlow

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  4. Albert F Parlow
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  6. Ilan R. Kirsch
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Good, D., Porter, F., Mahon, K. et al. Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Nat Genet 15, 397–401 (1997). https://doi.org/10.1038/ng0497-397

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