A novel hypothyroid 'growth-retarded' mouse derived from Snell's dwarf mouse

Area of Science:

• Endocrinology
• Genetics
• Developmental Biology

Background:

• The Snell's dwarf (DW/J) mouse model is a valuable tool for studying growth regulation.
• Understanding the genetic and hormonal factors influencing pubertal growth is essential for comprehending somatic development.

Purpose of the Study:

• To characterize a novel spontaneously derived mutant mouse with a distinct growth-retarded phenotype.
• To investigate the underlying genetic basis and hormonal mechanisms responsible for the observed growth delay and pubertal abnormalities.

Main Methods:

• Phenotypic characterization including growth patterns and hormonal analysis (pituitary GH, serum thyroxine).
• Histological and immunohistochemical examination of the anterior pituitary gland.
• Genetic analysis including breeding data for inheritance patterns and partial linkage analysis with microsatellite polymorphisms.

Main Results:

• The mutant mouse, termed 'growth-retarded mouse', displays a growth pause followed by delayed pubertal growth and delayed pituitary GH increase.
• Low thyroxine levels were observed from neonate to adulthood; tri-iodothyronine supplementation shortened the growth pause and initiated pubertal growth.
• Histology revealed unusual, non-reactive chromophobic cells in the enlarged anterior pituitary, with autosomal recessive inheritance (gene designated 'grm').

Conclusions:

• The 'grm' gene mutation disrupts normal pubertal development and somatic growth, likely through impaired pituitary-thyroid axis function.
• Evidence suggests a positive feedback interaction between the pituitary and thyroid glands is critical for maturing the hormonal network regulating pubertal growth and metabolism.
• The 'grm' gene is distinct from the lit and hyt genes, indicating a novel genetic locus involved in growth regulation.