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Generation of a novel mouse strain with conditional, cell-type specific, expression of DND1

Lisa Nunez1, Sharada Mokkapati2, Chengtai Yu3

  • 1Department of Pharmaceutical Sciences, Texas Southern University, Houston, Texas.

Genesis (New York, N.Y. : 2000)
|September 13, 2019
PubMed

Insights

Researchers developed a new transgenic mouse model to study Dead-End 1 (DND1) function in mammals. This model, LSL-FM-DND1flox/+, enables conditional DND1 expression, revealing its role in glucose regulation when ectopically expressed in the pancreas.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Dead-End 1 (DND1) is an RNA-binding protein essential for primordial germ cell viability in vertebrates.
  • DND1's function in mammalian systems, particularly wild-type DND1, requires further in vivo investigation beyond cell line studies.
  • Previous studies indicate DND1 can suppress cancer cell proliferation and enhance apoptosis.

Purpose of the Study:

  • To generate and characterize a novel transgenic mouse line for conditional, cell-type-specific expression of FLAG-myc-tagged wild-type DND1.
  • To facilitate in vivo studies of DND1's biological and molecular functions in mammalian systems.
  • To investigate the physiological effects of ectopic DND1 expression in specific tissues.

Main Methods:

  • Generation of the LSL-FM-DND1flox/+ transgenic mouse line.
  • Conditional expression of FLAG-myc-DND1 by combining LSL-FM-DND1flox/+ with Cre-recombinase expressing mouse strains.
  • Analysis of FLAG-myc-DND1 expression in various tissues.
  • Assessment of fertility and health effects in LSL-FM-DND1flox/+ mice.
  • Ectopic expression of FLAG-myc-DND1 in the pancreas and subsequent physiological analysis.

Main Results:

  • The LSL-FM-DND1flox/+ mouse line successfully enables cell type-specific expression of FLAG-myc-DND1 when combined with appropriate Cre-recombinase strains.
  • LSL-FM-DND1flox/+ mice are fertile and exhibit no apparent adverse health effects.
  • Chronic, ectopic expression of FLAG-myc-DND1 in the pancreas of older mice led to elevated fasting glucose levels.

Conclusions:

  • The novel LSL-FM-DND1flox/+ mouse model provides a valuable tool for studying the in vivo function of wild-type DND1.
  • Ectopic expression of DND1 in the pancreas may influence glucose homeostasis, suggesting a potential role in metabolic regulation.
  • This transgenic model opens new avenues for exploring DND1's involvement in various physiological processes and diseases.
Keywords:
FLAG-myc-DND1conditionaltransgenic LSL-FM-DND1 flox/+ mice

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