A structural gene (Hdc-s) for mouse kidney histidine decarboxylase

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• Histidine decarboxylase (HDC) enzyme concentration in mouse kidneys is influenced by hormones like estrogen, testosterone, and thyroxine.
• Genetic variations in HDC levels across mouse strains offer insights into enzyme structure, tissue-specific expression, and hormonal regulation.
• Differences in HDC structure, affecting cofactor binding and heat stability, have been observed between mouse strains.

Purpose of the Study:

• To investigate the genetic basis of variation in mouse kidney histidine decarboxylase (HDC) enzyme structure and concentration.
• To identify the genes and their linkage responsible for differences in HDC heat stability and enzyme levels.
• To map the location of the HDC gene complex on the mouse genome.

Main Methods:

• Analysis of histidine decarboxylase (HDC) enzyme properties (Km for pyridoxal-5'-phosphate, heat stability) in different inbred mouse strains.
• Crossbreeding experiments and analysis of recombinant inbred (RI) strains (BXD and BXH) to study inheritance patterns.
• Genetic mapping to determine the distance between the structural gene (Hdc-s) and the regulatory gene (Hdc).

Main Results:

• Identified two distinct phenotypes for HDC heat stability, determined by alleles Hdc-sb (heat-stable) and Hdc-sd (heat-labile).
• Demonstrated that these heat stability phenotypes are additively inherited.
• Found that the structural gene (Hdc-s) and a previously identified regulatory gene (Hdc) controlling kidney enzyme concentration are tightly linked (<0.685 cM apart) on mouse chromosome 2.
• These genes form part of the HDC gene complex, [Hdc].

Conclusions:

• The genetic variation in mouse kidney histidine decarboxylase (HDC) structure and concentration is controlled by at least two closely linked genes.
• The Hdc-s gene determines HDC heat stability, while the Hdc gene regulates kidney enzyme concentration.
• These genes are located within the HDC gene complex on chromosome 2, indicating a shared genetic basis for enzyme structure and regulation.