R. R. Fox

Genetic and physiological aspects of cholesterol accumulation in hyperresponding and hyporesponding rabbits.

After a 5 week period of feeding a cholesterol-rich diet to rabbits, hyperresponders with high plasma cholesterol levels and hyporesponders with low plasma cholesterol levels could be distinguished from normal responders. The response was found to be correlated with the esterase genotype at the Est-2 locus. The increase in total body cholesterol was higher in hyper- than in hyporesponders. In both groups most of the accumulated dietary cholesterol was found in plasma and liver. Adrenal weight and plasma corticosterone levels were more increased in hyper- than in hyporesponders. The cholesterol-rich diet resulted in an augmentation of liver lipase and lipoprotein lipase activities. These lipolytic activities were more increased in hyper- than in the hyporesponders.

Genetics of two tissue esterase polymorphisms (Est-4 and Est-5) in the rabbit

Two polymorphic esterase systems were found after electrophoresis of rabbit tissue homogenates. Each of these systems is controlled by an autosomal locus with two alleles. Est-4 determines the absence (Est-4a) or presence (Est-4b) of two bands of esterase activity with intermediate anodal mobility and broad substrate specificity. This polymorphism was found to be present in liver, small intestine, and spleen but not in kidney, heart, and testis. Est-5 is coding for cathodally migrating esterases which differ in mobility (Est-5a and Est-5b). This polymorphism was found only in kidney and testis homogenates. Est-5 esterases are more active against α-naphthyl acetate than against β-naphthyl acetate and have no activity against α-naphthyl butyrate. Linkage analysis indicated that Est-4 is localized on rabbit LG VI as part of a cluster of esterase loci, whereas Est-5 segregates independently. Rabbits from two inbred and nine partly inbred strains were tested for these polymorphisms.

Genetics of a tissue esterase polymorphism (Est-6) in the rabbit (Oryctolagus cuniculus)

Genetic analysis of a polymorphic tissue esterase revealed a new locus (Est-6) with two alleles (Est-6a andEst-6b) on linkage group VI of the rabbit.Est-6 is closely linked to theEst-1,2,4 cluster. Esterase ofEst-6 is found in many organs, particularly in liver and small intestine, but not in erythrocytes and serum.Est-6 esterase hydrolyzes α-naphthyl acetate and butyrate, naphthol AS-D acetate, indoxyl acetate, and butyrate as well as 5-bromoindoxyl acetate,N-acetyl-l-alanine-α-naphthyl ester but not 4-methylumbelliferyl acetate and fluorescein diacetate. The enzyme is inhibited by bis-p-nitrophenyl phosphate and eserine but not byp-chloromercuribenzoate. It was classified as a carboxylesterase (EC 3.1.1.1). Based on chromosomal localization, tissue distribution, substrate specificity, inhibitor sensitivity, and range ofpIs, rabbitEst-6 is assumed to be homologous with mouseEs-7.

Rabbit linkage group VIII: The alleles of the prt gene

The prt gene which is linked to the rabbit immunoglobulin κ-light chain gene, ab, has two phenotypes, PRT+ and PRT−. These phenotypes can be distinguished only when serum proteins from different rabbits are separated by polyacrylamide gel electrophoresis. The serum protein profiles for PRT+ rabbits show a band that is located on the anodal side of transferrin. This band is missing in the serum profiles of PRT− rabbits. However, the PRT protein is present in these rabbits. An antiserum which reacts with PRT from PRT+ rabbits detects two electrophoretic variants of PRT which are located in areas of the polyacrylamide gel obscured by other serum proteins. These results and other suggest that the prt gene has three alleles, the prta allele encoding the protein found in PRT+ rabbits and the prtb and prtc alleles encoding the two electrophoretic variants found in PRT− rabbits.

Separation of beta-D-galactosidases in rabbit tissues: genetics of neutral beta-D-galactosidase.

Three different types of β-d-galactosidase (EC 3.2.1.23) could be distinguished in rabbit tissues using electrophoretic procedures. (1) Acid β-d-galactosidase with a low mobility and maximal activity atpH 3–5 was found in the particulate fraction of various tissue homogenates. This enzyme hydrolyzed 4-methylumbelliferyl-d-galactoside, but no activity against other glycoside substrates could be demonstrated. The enzyme was inhibited by galactono-(1 → 4)-lactone. (2) Lactose-hydrolyzing β-d-galactosidase with an intermediate mobility was found only in juvenile small intestine. Most of the activity was found in the particulate fraction of the cell. The enzyme hydrolyzed several other synthetic glycoside substrates besides lactose. It was most active atpH 5–6 and strongly inhibited by glucono-(1 → 5)-lactone but not much affected by galactono-(1 → 4)-lactone. (3) Neutral β-d-galactosidase with a fast mobility and maximal activity atpH 6–8 was found in the soluble fraction of homogenates from liver, kidney, and small intestine. This enzyme also showed a broad substrate specificity; it possessed activity against aryl-β-d-glucoside, -fucoside, and -galactoside substrates but not against lactose. The enzyme was strongly inhibited by glucono-(1 → 5)-lactone and (less) by galactone-(1 → 4)-lactone. Neutral β-d-galactosidase and neutral β-d-glucosidase (EC 3.2.1.21) are probably identical enzymes in the rabbit. Individual variation, in both electrophoretic mobility and activity, was found for neutral β-d-galactosidase. Genetic analysis of the electrophoretic variants revealed that two alleles at an autosomal locus are responsible for this variation.

Fibrinogen concentration in the aqueous humor of buphthalmic rabbits

Fibrinogen concentration in the aqueous humor of buphthalmic rabbits, AXBU/J, and those of the normal parent strain AX/J are 0.36 +/- 0.14 and 0.08 +/- 0.01 mg/ml, respectively. There was no detectable fibrinogen in the aqueous humor of normal inbred strain III/J rabbits. Among the buphthalmic rabbits, elevated fibrinogen concentration in the aqueous humor was observed in two month old prodromal rabbits, indicating a small leakage of fibrinogen into the anterior chamber before the development of buphthalmia. Protein concentration in the aqueous humor was close to normal, in spite of an elevated level of fibrinogen in the young buphthalmic rabbits. Severe protein leakage was seen in only some of the old buphthalmic rabbits.