Marked Sex-related Differences Research Articles

Proteomic analysis of the left-ventricular myocardium implies marked sex-related differences in mitochondrial and cytoskeletal adaptation to long-term endurance exercise in a rat model

Proteomic analysis of the left-ventricular myocardium implies marked sex-related differences in mitochondrial and cytoskeletal adaptation to long-term endurance exercise in a rat model

The Modulatory Effects of DMF on Microglia in Aged Mice Are Sex-Specific

There is a striking sex-related difference in the prevalence of many neurodegenerative diseases, highlighting the need to consider whether treatments may exert sex-specific effects. A change in microglial activation state is a common feature of several neurodegenerative diseases and is considered to be a key factor in driving the inflammation that characterizes these conditions. Among the changes that have been described is a switch in microglial metabolism towards glycolysis which is associated with production of inflammatory mediators and reduced function. Marked sex-related differences in microglial number, phenotype and function have been described in late embryonic and early postnatal life in rodents and some reports suggest that sexual dimorphism extends into adulthood and age and, in models of Alzheimer’s disease, the changes are more profound in microglia from female, compared with male, mice. Dimethyl fumarate (DMF) is a fumaric acid ester used in the treatment of psoriasis and relapsing remitting multiple sclerosis and, while its mechanism of action is unclear, it possesses anti-inflammatory and anti-oxidant properties and also impacts on cell metabolism. Here we treated 16–18-month-old female and male mice with DMF for 1 month and assessed its effect on microglia. The evidence indicates that it exerted sex-specific effects on microglial morphology and metabolism, reducing glycolysis only in microglia from female mice. The data suggest that this may result from its ability to inactivate glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

We Must Talk about Sex and Focal Dystonia

In a recent workshop on "Defining research priorities in dystonia,", there was absolutely no reference to sex as a factor in disease pathogenesis. In this viewpoint paper, we argue that the most distinctive aspects of adult onset isolated focal dystonia are the marked sex-related differences demonstrated by epidemiological, clinical, and laboratory studies in patients with adult onset dystonia, particularly in cervical dystonia, the most common presentation. We propose that the future focus of research should be on neurobiological mechanisms underlying the profound sexual dimorphism in this disorder. Targeting research into gamma aminobutyric acid (GABA)ergic function, which also shows similar sexual dimorphism, would be most productive in elucidating the pathogenesis of adult onset dystonia. © 2021 International Parkinson and Movement Disorder Society.

Significant effects of sex, strain, and anesthesia in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy.

The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy is increasingly being used for studies on epileptogenesis and antiepileptogenesis. Almost all previous studies used male mice for this purpose, and no study is available in this or other models of acquired epilepsy that directly compared epileptogenesis in female and male rodents. Epidemiological studies suggest that gender may affect susceptibility to epilepsy and its prognosis; therefore, one goal of this study was to investigate whether sex has an influence on latent period and epileptogenesis in the intrahippocampal kainate model in mice. Another aspect that was examined in the present study was whether mouse strain differences in epileptogenesis exist. Finally, we examined the effects of different types of anesthesia (chloral hydrate, isoflurane) on kainate-induced status epilepticus (SE) and epileptogenesis. Continuous (24/7) video-EEG monitoring was used during SE and the 2 weeks following SE as well as 4-6 weeks after SE. In male NMRI mice with chloral hydrate anesthesia during kainate injection, SE was followed by a seizure-free latent period of 10-14 days if hippocampal paroxysmal discharges (HPDs) recorded from the kainate focus were considered the onset of epilepsy. Anesthesia with isoflurane led to a more rapid onset and higher severity of SE, and not all male NMRI mice exhibited a seizure-free latent period. Female NMRI mice differed from male animals in the lack of any clear latent period, independently of anesthesia type. Furthermore, HPDs were only rarely observed. These problems were not resolved by decreasing the dose of kainate or using other strains (C57BL/6, FVB/N) of female mice. The present data are the first to demonstrate marked sex-related differences in the latent period following brain injury in a rodent model of acquired epilepsy. Furthermore, our data demonstrate that the choice of anesthestic agent during kainate administration affects SE severity and as a consequence, the latent period, which may explain some of the differences reported for this model in the literature.

In vivo and in vitro evidence of the sex-dependent pharmacokinetics and disposition of G004, a potential hypoglycemic agent, in rats

G004 is a novel sulfonylurea hypoglycemic drug which aimed at reducing macro- and micro-vascular complications as well as controlling glucose excursion in type 2 diabetes mellitus. The pharmacokinetics of G004 in rats was sex- and dose-dependent over the dose range of 1-10mgkg(-1). The mean AUC values in the female rats were fivefold higher than those in males. Drug blood and tissue levels in female rats were higher than the most counterparts of males. Compared with male rats, G004 was eliminated slowly from female rats in the bile, urine and feces. Consistent with the in vivo observations, marked sex-related difference of the metabolizing activity between the male and female liver microsomes (RLM) was observed. The intrinsic clearance (V max/K m) of G004 was 3.1-fold larger in the RLM from male than female rats. Seventeen oxidative metabolites were identified in rat liver microsomes. The amount of three metabolites of G004 showed relatively sex-related difference in RLM incubations. CYP2C11 was demonstrated mainly contributing to the sex-related differences in the pharmacokinetics and disposition of G004 in rats.

Sex-Related Differences in Hypertension

Much of what we understand about the regulation of arterial pressure and extracellular fluid volume has been derived from studies in men. Although the responses that can be mounted against major physiological challenges to extracellular fluid volume (hemorrhage/dehydration) are essentially similar in men and women, there are marked sex-related differences in the regulation of renal and cardiovascular physiology. These possibly underpin the greater risk of renal and cardiovascular disease (CVD) in men and, conversely, confer the relative protection from these conditions in women, at least until menopause. In recent years, advances have been made in understanding the mechanistic bases for sex-related differences in CVD and these have been reviewed in detail.1–3 Therefore, the purpose of this report is to provide an update of findings in the past few years. Increasingly, studies are incorporating sex as a factor into their analyses. Although not all studies demonstrate a sex-specific interaction,4–7 many do, exemplifying the mantra, seek and ye shall find; this appears to be particularly true for sex-related differences in CVD. In recent years, evidence that women have smaller and stiffer hearts because of a greater collagen content has received a good deal of attention for the reason that it may explain some of the puzzling differences in clinical signs of CVD between men and women. Puntmann et al8 examined aortic stiffness by pulse wave velocity and ventricular deformation indices using MRI both at rest and during dobutamine challenge in elderly men and women. At rest, women had greater aortic stiffness and ventricular deformation than men. Moreover, sex-related differences were observed during stress because men had increased longitudinal and circumferential ventricular deformation during dobutamine challenge, whereas women only had an increase in circumferential deformation.8 These data suggest that differential loading of the aortic reservoir …

Age and sex estimation by metric measurements and fusion of hyoid bone in a Turkish population

The hyoid bone is of great importance in forensic medicine practice and it has been studied for various forensic purposes; however, there have been few studies dealing with age and sex estimation using the hyoid bone. Using discriminant function analysis this study attempts to determine the utility of metric measurements and non-metric variations of the hyoid bone in terms of estimation of sex and age in a Turkish population and to find out differences with other populations by comparison of obtained results with the literature. For this purpose, the hyoid bones of 85 cadavers of known sex and age were extracted and 33 measurements were made with a computer program following photography with a camera. In addition to these measurements, the degree of fusion of the greater cornua to the hyoid corpus was examined. Out of 33 measurements, 18 showed significant sex-related differences.There was a sharp rise in hyoid bone fusion in both males and females after the age of 60 years. However, no marked sex-related differences were observed regarding fusion. The unstandardised canonical discriminant function was estimated based on three variables, and the correct classification ratio was 77.4% for males and 81.3% for females. The obtained findings suggest that measurements of hyoid bone can be used for sex estimation in the Turkish population.

Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms.

Metabolism of Pyridalyl in Rats

Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] was examined in male and female Sprague-Dawley rats. After a single oral administration of [dichlorophenyl-(14)C]pyridalyl at 5 or 500 mg/kg, the (14)C concentration in blood reached maxima at 2 to 10 h and then decreased rapidly with a biological half-life of approximately 11 to 12 h. (14)C concentrations in liver, fat, adrenal gland, and spleen were relatively high at a low dose, reaching 2.3 to 2.7, 1.9 to 2.3, 1.1 to 1.9, and 1.4 ppm, respectively, in these tissues at 2 to 24 h after administration. Although (14)C elimination from fat and hair and skin was relatively slow compared with that from other tissues, the total residue on the 7th day was low, in the range of 1.3 to 2.3% of the dose. The (14)C distribution in tissues with a high dose, as examined by whole-body autoradiography, was similar to that observed for the low dose. Results revealed that more than 88% of the dosed radiocarbon was excreted within 1 day after administration, with cumulative (14)C excretion into urine and feces 7 days after administration of 1.7 to 2.6 and 98.7 to 101.7%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and mass spectrometry. Residual (14)C in fat was extracted, and analysis by thin-layer chromatography showed it to be due to pyridalyl itself. No marked sex-related differences were observed in (14)C elimination, (14)C distribution, and metabolites.

A Morphometric Study of Age-Related Changes in Adult Human Epiglottis Using Quantitative Digital Analysis of Cartilage Calcification

The epiglottis plays an important role in deglutition in humans. The present study investigated age-related changes in the epiglottis using macroscopic and microscopic measurements. Epiglottic specimens from 281 Japanese adult cadavers (177 males, 104 females) were obtained. Specimens were divided into three groups according to age: group I: 20–39 years old (32 males, 26 females), group II: 50–69 years old (82 males, 36 females), and group III: 80–98 years old (63 males, 42 females). Width, height, and thickness were measured macroscopically. To evaluate the degree of calcium deposition, the calcium volume in digitalized von Kossa-stained sections was assessed using a quantitative analysis. An elemental analysis of the area detected with von Kossa staining was done using energy-dispersive X-ray fluorescence spectrometer (EDX). Measurements of the thickness and cell density in the superficial and deep layers of epiglottic cartilage were performed in horizontal histological sections. No significant differences in macroscopic width or height were found across the age groups in either sex. A series of three measurements in males was significantly larger than in females (p < 0.05). The volume of the calcium deposit area was greater in males than in females (p < 0.05) and was significantly increased in group III in males (p < 0.05). The lower level of the epiglottic cartilage showed a greater calcium deposit area than the upper level. In the scanning image by line and surface analysis using EDX, the calcium deposit areas detected with von Kossa staining indicated a close association of calcium and phosphorus ions. The mean Ca/P molar ratio in the calcium deposit area was 1.32 ± 0.12. Microscopic cartilage thickness increased significantly with age (p < 0.05), and was greater in males than in females (p < 0.05). Cartilage cell density in the superficial cartilage layer was higher than in the deep layer and was decreased in group III (p < 0.05). Cartilage cell density was lower in males compared to females. Diameter of chondrocytes significantly increased in group III (p < 0.05) and was larger in males than in females in group III (p < 0.05). Epiglottic cartilage exhibited marked sex-related differences and progression of calcification with age. Calcification of epiglottic cartilage in elderly individuals may affect movement patterns in deglutition.

17β-Estradiol Improves Survival in Male Mice with Cardiomyopathy Induced by Cardiac-Specific Tumor Necrosis Factor-α Overexpression

A transgenic mouse model of congestive heart failure (CHF) consequent to cardiac-specific overexpression of tumor necrosis factor-alpha (TNF-alpha) (TNF1.6) displays marked sex-related phenotypic differences. To clarify the potential contributions of estrogen to these sex-specific differences, male TNF1.6 mice were treated with 17beta- estradiol (E2). E2 treatment started at 25 +/- 1 days old (group A), but not at 36 +/- 2 days old (group B), significantly improved survival rate (p < 0.05). Furthermore, ventricular weight/body weight ratio was significantly decreased by E2 treatment in group A (p < 0.05). Echocardiography revealed that E2-treated hearts in group A exhibited less left ventricular dilatation (p < 0.05) relative to untreated male TNF1.6 mice (control). Moreover, in group A, E2 treatment partially reversed basal and isoproterenol-stimulated fractional shortening in TNF1.6 mice (p < 0.05). The cardiac content of TNF-alpha and interleukin-1beta (IL-1beta) was not changed by E2 treatment regardless of the timing of treatment. Thus, E2 exposure prior to puberty can limit the severity of cardiomyopathy in male TNF1.6 mice.

Sex-related differences in blood and gonad levels of testosterone in silver fox fetuses

The mass of silver fox fetuses of both sexes, their gonads, and adrenals, and the levels of testosterone in blood serum and in gonads and adrenals were determined from day 31 of gestation and every five days thereafter until its termination. Marked sex-related differences were revealed: the blood and gonad levels of testosterone in male fetuses were much higher than those in female fetuses. The fetal adrenals contained significantly less testosterone than the gonads. No sex-related differences in the content of testosterone in the fetal adrenals were found. No differences were found in the body and adrenal mass in female and male fetuses at all the developmental stages studied, while the mass of ovaries exceeded that of testes from day 45 of gestation. The data obtained suggest sex dimorphism in the production of testosterone by gonads in silver foxes appears after day 35 and appears to correspond to the period of morphological differentiation of gonads.

The sero-epidemiology of diphtheria in Western Europe. ESEN Project. European Sero-Epidemiology Network.

Seven countries in Western Europe collected large, representative serum banks across the entire age range and tested them for diphtheria anti-toxin (sample size ranged from 2991 to 7715). Although a variety of assays were used, the results were all standardized to those of a reference laboratory and expressed in international units. The standardization process, and the availability of similar, large data sets allowed comparative analyses to be performed in which a high degree of confidence could be ascribed to observed epidemiological differences. The results showed that there were large differences in the proportion of adults with insufficient levels of protection amongst different countries. For instance, roughly 35% of 50- to 60-year-olds were found to be seronegative (titre < or = 0.01 IU/ml) in Finland compared with 70-75% in the United Kingdom. Furthermore, the proportion of seronegative adults would be expected to increase in some countries, notably Italy and the western part of Germany. In those countries with vaccination of military recruits there was a marked sex-related difference in the proportion of seropositive individuals. All countries have high levels of infant vaccine coverage (> 90%) but the accelerated schedule in the United Kingdom appears to result in lower anti-toxin titres than elsewhere. In Sweden, booster doses are not offered until 10 years of age which results in large numbers of children with inadequate levels of protection. Although the United Kingdom and Sweden both have higher proportions of seronegative children than elsewhere the likelihood of a resurgence of diphtheria in these countries seems remote.

Gender Differences in the Reinforcing Properties of Morphine

The purpose of the present studies was to examine whether gender differences could be observed in an important aspect of morphine's pharmacology: its reinforcing properties. Our results showed that morphine served as a positive reinforcing agent in both male and female rats in a place conditioning paradigm, but that the dose–response curves displayed marked sex-related differences. At doses from 0.2 up to 10.0 mg/kg, morphine induced an equally strong preference for the drug-associated chamber in males and females. However, as the dose was increased from 10–17.5 mg/kg, morphine ceased to act as a positive reinforcer in males. In contrast, a very strong preference for the morphine-associated chamber was still observed in females at doses up to 30 mg/kg. No gender differences in the blood and brain levels of morphine were observed subsequent to morphine administration during the conditioning phase, suggesting that pharmacokinetic factors were not involved in the sex-related differences observed. Consequently, these results suggest that there are intrinsic sex-linked differences in the doses of morphine that can induce a preference for the drug-associated chamber in a place-conditioning paradigm that are most likely related to differences in the sensitivity of the central nervous system to morphine's reinforcing properties in males and females.

Sexual Dimorphism in Phagocytic Activity of Wall Lizard's Splenic Macrophages and Its Control by Sex Steroids

The splenic macrophages of wall lizards exhibited marked sex-related difference in their phagocytic activity. The percentage phagocytosis and phagocytic index in females was considerably higher than that of males. Gonadectomy resulted in significant increase in percentage phagocytosis and phagocytic index in both male as well as female lizards, suggesting that gonadal hormones inhibit macrophage phagocytosis. This was further confirmed by dose and time-related in vivo and in vitro experiments in which DHT suppressed phagocytosis which increased with dose or duration of treatment, while E2 either suppressed or had no effect on phagocytosis, depending on dose and duration of treatment. Exposure of macrophages to steroid receptor antagonists, cyproterone acetate (CPA), or tamoxifen citrate (Tam) prior to treatment with their respective sex steroids markedly reduced the DHT- or E2-modulated suppression of macrophage phagocytosis. It is concluded that the sex steroids modulate splenic macrophage phagocytosis via receptor-mediated systems.

Sexually dimorphic expression of sst1 and sst2 somatostatin receptor subtypes in the arcuate nucleus and anterior pituitary of adult rats.

The pattern of growth hormone (GH) secretion and rate of somatic growth are markedly sexually dimorphic, but the underlying neuroendocrine mechanisms are far from clear. In the present study, we tested the hypothesis that the sexual dimorphism of GH secretion may be due to gender-related differences in the transduction of somatostatin's actions in brain and/or pituitary. To accomplish this, we compared the distributional pattern and level of expression of two somatostatin receptor subtypes, sst1 and sst2, in the brain and pituitary of adult male and female rats by in-situ hybridization using 35S-labelled antisense riboprobes. In the brain, the hybridization pattern and labelling density of sst1 and sst2 mRNA-expressing cells, as revealed by computer-assisted image analysis, in areas including the cerebral cortex, medial habenula (MHb) and ventromedial hypothalamic nucleus (VMN), were similar in male and female rats. In contrast, there was a marked sex-related difference in sst1 expression in the arcuate nucleus of the hypothalamus; both the number and labelling density of sst1 mRNA-expressing cells were two- to threefold greater in males than in females and this significant increase was homogenous throughout the rostrocaudal extent of the nucleus. No gender-related differences in arcuate sst2 mRNA levels were found. At the level of the anterior pituitary, the labelling density of sst2 mRNA in males was significantly higher than that of females. No sex-related difference in pituitary sst1 mRNA was observed. These results demonstrate a sexual dimorphism in the expression of two somatostatin receptor subtypes, sst1 and sst2, at the level of the arcuate nucleus and anterior pituitary, respectively. Such dimorphism suggests a differential involvement of sst1 and sst2 in GH regulation with respect to gender, and may imply roles for sst2 and sst1 in transducing somatostatin's actions on pituitary somatotrophs and GH-releasing hormone-containing arcuate neurones, respectively, to generate the lower basal and higher GH pulse levels characteristic of the male rat.

Metabolism of Pyriproxyfen in Rats. 1. Absorption, Disposition, Excretion, and Biotransformation Studies with [phenoxyphenyl-14C]Pyriproxyfen

Male and female rats were given a single oral dose of [phenoxyphenyl- 14 C]pyriproxyfen [4-phenoxyphenyl (R,S)-2-(2-pyridyloxy)propyl ether] at 2 (low dose) or 1000 (high dose) mg/kg. 14 C was rapidly excreted into feces and urine, with the former route predominating (about 90% of the dose). Peak 14 C concentrations in blood, kidney, liver, and other tissues except for fat occurred 2-8 h after administration, being 0.4, 0.4, 2.5, and <0.2 μg of pyriproxyfen equivalents/g of tissue (ppm), respectively. Peak 14 C concentration in fat occurred 12-24 h after administration, being 0.3-0.5 ppm. 14 C tissue residues on the seventh day were below 0.02 and 10 ppm for the low and high doses, respectively. The major metabolic reactions were hydroxylation at the 2- or 4-position of the terminal phenyl ring, hydroxylation at the 5-position of the pyridyl ring, cleavage of the ether linkages, and conjugation of the resultant phenols with sulfuric acid. No marked sex-related differences were observed for 14 C excretion or 14 C tissue residues. However, a slight sex-related variation was found for the extent of metabolic reactions

Butyrylcholinesterase from intestinal epithelial cells of quail, chick and duck: A comparative study during development

1. 1. Epithelial cells of avian intestine express non-specific cholinesterase (butyrylcholinesterase, BuChE) activity both in the embryo and adult animal. 2. 2. Quail, duck and chick exhibit increased BuChE activity during the late embryonic period followed by decreased activity. The minimum value is reached after hatching at day 1 in quail, day 4 in chick and day 6 in duck. 3. 3. The three species display marked sex-related differences mainly during the peri-hatching period. BuChE activity is higher in females than in males. 4. 4. The three globular forms, G 1, G 2 and G 4, are detected during the last days of embryonic development. After hatching, changes in the relative amounts of these forms are related to the disappearance of G 2 and the gradual decrease of G 4. In adult quail and duck, G 4 is not detected and BuChE activity corresponds only to the G 1 form. 5. 5. The changes in BuChE activity and distribution of the molecular forms occur in a similar manner in all three species although the embryonic periods differ notably, suggesting that hormonal factors secreted during this period and involved in the preparation of hatching may regulate BuChE activity.

Effects of chronic administration of perfluorooctanoic acid on fatty acid metabolism in rat liver: Relationship among stearoyl-coenzyme A desaturase, 1-acylglycerophosphocholine acyltransferase, and acyl composition of microsomal phosphatidylcholine.

Male and female rats were fed on a diet containing 0.01% (w/w) perfluorooctanoic acid (PFOA) for 2, 22, or 26 weeks and effect of PFOA on activities of microsomal 1-acylglycerophosphocholine acyltransferase, microsomal stearoyl-coenzyme A (CoA) desaturase, peroxisomal beta-oxidation and on acyl composition of microsomal phosphatidylcholine in liver were studied. The treatment of male rats with PFOA for 2 weeks caused increases in the activities of stearoyl-CoA desaturase, 1-acylglycerophosphocholine acyltransferase, and peroxisomal beta-oxidation. The elevated activities of microsomal 1-acylglycerophosphocholine acyltransferase and peroxisomal beta-oxidation were unchanging throughout the long-term treatment. The induced activity of microsomal 1-acylglycerophosphocholine acyltransferase was found to be highly correlated with the induced activity of peroxisomal beta-oxidation. In contrast to these two enzymes, the increased activity of stearoyl-CoA desaturase by the short-term treatment of rats with PFOA did not last for 26 weeks, although the activity in rats treated for the long-term was higher than that of age-matched controls. The treatment of male rats with PFOA caused great alterations in the acyl composition of microsomal phosphatidylcholine. The high correlation seen between proportion of 18:1 in the C-2 position of phosphatidylcholine and activities of both stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase suggest that these two enzymes participate actively in the regulation of acyl composition of phosphatidylcholine in rat liver. The present results show that hepatic responses to PFOA remain consistent throughout the period of the administration, but the elevated activities of the hepatic enzymes and the altered acyl composition of microsomal phosphatidylcholine returned to control levels within 4 weeks after PFOA was withdrawn from the diet. Even after the chronic administration of PFOA, these parameters of female rats responded only slightly to the challenges by the chemical, which indicates a marked sex-related difference being still apparent in the response of rat liver to PFOA.

Mouse carbonic anhydrase III: Nucleotide sequence and expression studies

A cDNA for the mouse carbonic anhydrase, CAIII, has been isolated from a lambda gt11 expression library. The cloned cDNA contains all of the coding region (777 bp) and both 5' untranslated (86-bp) and 3' untranslated (217-bp) sequences. The coding sequence shows 87% homology at the nucleotide level and 91% homology, when amino acid residues are compared, with human CAIII. Protein and mRNA analyses show that CAIII is present at low levels in cultured myoblasts and is abundant in adult skeletal muscle and in liver. The marked sex-related differences in CAIII distribution, described for rat liver, are not seen in the mouse. Restriction fragment length polymorphisms using TaqI and PstI are described which distinguish between Mus spretus and Mus musculus domesticus.