Initial characterization of a new miniature animal model in the rat: studies on anatomy, pituitary hormones and GH mRNA in miniature rat Ishikawa

Abstract

Miniature rat Ishikawa (MRI) is an experimental model for pituitary miniaturism with an autosomal recessive mode of inheritance. This paper reports the discovery and initial characterization of a new mutant rat. The mutation arose spontaneously in a breeding colony of Wistar rats at the Ishikawa Animal Laboratory (Saitama). Body growth in MRI was retarded in 56% and 71% of normal control rats for males and females, respectively. In immunohistochemical studies for anterior pituitary sections, GH secreting cells were reduced in the amounts and the intensity of stain in MRI compared with normal control rats. There was no detectable difference in the amounts or distribution of LH, FSH, PRL, TSH and ACTH between MRI and normal control rats. MRI showed a selective reduction in pituitary GH contents and in response to human GRH. Pituitary GH contents were approximately 31% of normal in males and 45% in females. Pituitary TSH contents and serum TSH levels were within the normal range in MRI. Total T3 and T4 levels were also within the normal range in MRI. Pituitary total mRNA extracts revealed that GH message in male MRI was reduced in 53% of normal control rats, and that fragment size of GH mRNA was within the normal range. The immunohistochemical findings, supported by a reduced GH content in pituitary extracts and low GH response to GRH, were compatible with a deficiency of GH caused by a reduced expression of pituitary GH mRNA. MRI, which showed a selective pituitary GH deficiency, may provide a useful new model for studying the endocrinological aspects of the growth.