• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM.

Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet beta cell number and impaired beta cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, beta cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and beta cell function in disease pathogenesis.

Pubmed ID: 15286800


  • Ma D
  • Shield JP
  • Dean W
  • Leclerc I
  • Knauf C
  • Burcelin R RĂ©
  • Rutter GA
  • Kelsey G


The Journal of clinical investigation

Publication Data

August 2, 2004

Associated Grants


Mesh Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Blood Glucose
  • Diabetes Mellitus, Type 2
  • Disease Models, Animal
  • Genomic Imprinting
  • Homeostasis
  • Humans
  • Hyperglycemia
  • Immunohistochemistry
  • In Situ Hybridization
  • Insulin
  • Islets of Langerhans
  • Mice
  • Mice, Transgenic
  • Pancreas
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution
  • Transcription, Genetic