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Trichinella spiralis infection in mice. Mechanism of the resistance in animals genetically selected for high and low antibody production.

Mice genetically selected according to their capacity to produce antibody were orally infected with fifty muscle larvae. After 1 month, the number of larvae found in low responder mice was twice the number found in high responder mice. Following a second infection, low responder mice were completely protected while high responder mice showed only partial protection. It is suggested that the better resistance of high responder mice after a primary infection is due to their high and rapid antibody production. However, at the time of a secondary infection both lines of mice possess enough antibody to act on the effector cells (macrophages, eosinophils, etc.) and resistance is then dependent on the metabolic activity of these cells, which is more intense in the low responder mice.

Animals

Genetic selection of mice for quantitative responsiveness of lymphocytes to phytohemagglutinin.

A two-way selection was performed in mice according to the quantitative in vitro response of lymph node lymphocytes to the mitogenic activity of phytohemagglutinin (PHA). The foundation population was composed of outbred mice produced by reciprocal mating of equal numbers of mice from four different colonies. The selective breeding was carried out by mating of mice at each generation giving the best or the lowest response, respectively. The progressive interline separation produced by 6 generations of selective breeding demonstrates that responsiveness to PHA is submitted to polygenic regulation. The heritability of the character investigated is 0.28 +/- 0.08. The interline separation is also found with another T mitogen, concanavalin A (Con A). In spleen cells PHA and Con A produce a similar interline difference. In contrast, the purified protein derivative of tuberculin (PPD) stimulated both lines equally, and E. coli lipopolysaccharide gave only a slightly higher response in high line. This finding implies that our selection based upon response to PHA did not influence B cell function.

Animals

Genetic selection for diabetogenic traits in Yucatan miniature swine.

Yucatan miniature pigs have been selectively bred for reduced and increased glucose clearance during an intravenous glucose tolerance test. Pigs with low glucose clearance rates (low K) have been selected through the F-5 generation. They have a significantly reduced rate of glucose clearance and a blunted peripheral IRI increase in response to the challenge. Through the F-5 generation, heritability of glucose tolerance is estimated at 0.26. Sporadic fasting blood glucoses in excess of 100 mg/dl are seen in later generations of this group. High glucose clearance pigs (high K) have been selected through the F-4 generation. They have significantly increased rates of glucose clearance and a greater increase in peripheral IRI than the low K animals. The estimated heritability for high K through the F-4 generation is 0.31. No evidence of fasting hypo- or hyperglycemia has been seen in the high K animals.

Animals

An improved procedure for genetic selection against hip dysplasia in dogs.

Rapid weight gain can educe hip dysplasia of dogs with normal hip joints. It is proposed that progeny whose parents have "excellent genotypes" would not be susceptible to this stress and would develop normal hip joints. The method for reducing the incidence of hip dysplasia in dogs would be to use stress to identify carriers (parents) and potential carriers (progeny), and select for breeding only dogs with proved genotypic value and those progeny with the best hip joint conformation.

Animals

[Genetic selection of mice for quantitative responsiveness of lymphocytes to phytohemagglutinin].

A two-way selection was performed in mice according to the quantitative response of small lymphocytes to the mitogenic activity of phytohaemagglutinin (PHA). The response of inguinal lymph node cells of each mouse to an optimal dose of PHA was measured by 3H-thymidine incorporation using a micro-plate method. Starting from four outbred mouse strains we mated on the one hand mice getting the best response and on the other hand mice getting the poorest response. A progressive separation of the two lines was observed. At the 7th generation a 3-fold difference was found between the two lines. A similar interline difference was observed when concanavalin A (ConA) was used as mitogen. The separation of the two lines was also evident when spleen cells or thymus cells were cultured with PHA or ConA.

Animals

Risk factors in pigeons genetically selected for increased atherosclerosis susceptibility.

A strain of genetically selected White Carneau pigeons (WC-2) with increased atherosclerosis at similar plasma cholesterol concentrations as randomly bred (RBWC) pigeons was studied to evaluate the commonly known risk factors for atherosclerosis. Indicators for the presence of hypertension, diabetes mellitus, "stress", hyperuricemia and hypothyroidism were determined. In pigeons fed the atherogenic diet, major differences in atherosclerosis were seen between WC-2 and RBWC. WC-2 pigeons had more aortic surface covered with plaque and greater concentrations of aortic nonesterified cholesterol, esterified cholesterol, uronic acid, and hydroxyproline, as well as a greater prevalence and severity of coronary artery atherosclerosis. For WC-2 and RBWC pigeons we found similar levels of hypercholesterolemia, mean blood pressure, plasma triglyceride and glucose concentrations. In addition, several other physiological variables such as plasma uric acid, calcium and phosphorus concentrations, adrenal and thyroid weights which have been implicated in the pathogenesis of atherosclerosis were similar. The findings indicate that the differences in extent and severity of atherosclerosis between WC-2 and RBWC cannot be explained by differences in the risk factors studied. Possible genetic regulation of atherosclerosis by mechanisms operable in the arterial wall of WC-2 pigeons is suggested.

Animals

Some models of genetic selection.

This paper begins with a description of the classical theory of viability selection in which probabilities that individuals of various genotypes survive are in proportions that do not change with time and are independent of population structure. Salient features of viability selection with one and two loci are reviewed. This theory is intimately connected with the usual theory of mass selection in quantitative genetics. It is well known that the mean of the relative viabilities does not necessarily increase if there is viability selection at more than one locus. It also turns out that if there is selection for fecundity with one locus, the mean fecundity may steadily decrease or oscillate rather than increase. This and the fact that a Hardy-Weinberg structure may no longer exist at any stage of life may have a bearing on predicting progress from artificial selection on reproductive characters. Classical viability selection theory does not completely describe natural selection. Other possibilities are discussed. Among these is the density and frequency dependent selection induced when the population lives in a limited habitat. Implications in quantitative genetics are discussed.

Alleles

Genetically selected winner and loser rats: what was selected?

Throughout the 6--12th generation, genetically selected winner and loser rats in the straight runway test, were studied, in relation to weight, open field behavior, behavioral responses to footshock and adrenocortical response following stimulation. The results showed that the Loser Runway Strain (LRS) when compared to the Winner Runway Strain (WRS), were (1) lighter in weight, (2) defecated less, ambulated more and showed higher frequency of rearing-up when submitted to an open field (3) defecated less and jumped more in reaction to footshock and (14) had a higher rise of corticosterone levels following handling or footshock. These differences between WRS--LRS are the same found between male-female rats. This conclusion does not favor the validity of the runway test as a social measure, and suggests that WSR--LRS were selected according to male-female characteristics instead of a winning or losing trait.

Animals

Trichinella infestation in mice genetically selected for high and low antibody production.

Mice genetically selected according to their capacity to produce antibodies (high and low responder lines) were infested with Trichinella spiralis. High responder mice produced much higher levels of IgE and gamma1 serum antibodies than low responder mice. IgG and IgM antibodies were detected by immunodiffusion analysis or passive haemagglutination only in animals of the high responder line and in very low concentrations. The number of living larvae present in the muscles was very similar in the animals of both lines 30, 60 or 75 days after infestation.

Animals

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol.

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.

Animals

CRISPR/Cas9-compatible plasmids enabling seven dominant genetic selection methods for the human fungal pathogen Cryptococcus neoformans.

Cryptococcus neoformans is the most common cause of human fungal meningitis and an important model system for studying fundamental eukaryotic biology. Genetic manipulation of this organism relies on three dominant drug resistance markers (nourseothricin acetyltransferase [NAT], neomycin phosphotransferase II [NEO], and hygromycin B phosphotransferase [HYG]) and the recyclable dominant prototrophic marker amdS. With ongoing technological advances that are expanding our ability to explore cryptococcal gene function, contemporary studies often require multiple genetic manipulations in the same strain. Additional dominant selection methods would maximize the utility of these tools by facilitating their combinatorial use. Here, we identify blasticidin S resistance via the blasticidin S deaminase (BSD) or blasticidin S resistance (BSR) markers as a novel dominant selection method for C. neoformans. We further validate phleomycin resistance via the bleomycin resistance gene (BLE) marker as an additional selection method, confirming a study that first established this marker 25 years ago (J. Hua, J. D. Meyer, and J. K. Lodge, Clin Diagn Lab Immunol 7:125-128, 2000, https://doi.org/10.1128/cdli.7.1.125-128.2000). To enable highly efficient CRISPR/Cas9-mediated genome modification, we incorporated these markers, as well as the newly established dominant prototrophic marker ptxD (M. Khongthongdam, T. Phetruen, and S. Chanarat, Microbiol Spectr 13:e01618-24, 2025, https://doi.org/10.1128/spectrum.01618-24), into a vector series that enables the construction of fused marker-sgRNA products via PCR. Altogether, this work expands the number of dominant genetic selection methods for C. neoformans to seven, including five drug selection regimes and two prototrophic methods. The vector series has been deposited at Addgene. IMPORTANCE Cryptococcus neoformans is the top-ranked World Health Organization priority fungal pathogen due to its widespread distribution and inadequate treatment options. Additionally, as a basidiomycete yeast occupying an underexplored branch of the fungal kingdom, this organism is a powerful system for deciphering core eukaryotic biology that is absent in classic model fungi. Defining functions for novel cryptococcal genes is a crucial priority, and the availability of additional genetic selection methods would facilitate these efforts. In this study, we establish blasticidin S resistance as a novel genetic selection method for C. neoformans, and we validate a previous report using phleomycin resistance as such. This work expands the number of reliable dominant selection methods to seven, providing flexibility for the introduction of sequential genetic modifications into single strains.

Cryptococcus neoformans

Aortic glycopeptide sialic acid, hexose and hexosamine in a genetically selected (WC-2) strain of atherosclerosis-susceptible pigeon.

The aortic content of glycopeptide sialic acid, hexosamine and hexose was studied in a genetically selected strain of White Carneau pigeons (WC-2) with significantly more severe atherosclerosis than randomly bred White Carneau pigeons (RBWC). Pigeons were fed an atherogenic diet for 3 months and examined to determine differences in content of glycopeptide-sugars between WC-2 and RBWC, changes with the progression of atherosclerosis and the relationship of aortic cholesterol to glycopeptide-sugar content. In animals with mainly normal aorta (cholesterol content of 0.2-0.3 mg/cm2-aorta) sialic acid was significantly lower in WC-2 pigeons. The progression of atherosclerosis was associated with increased aortic glycopeptide sialic acid (r = 0.78; p less than 0.05) in WC-2 pigeons whereas an inverse relationship was suggested in RBWC pigeons. In WC-2, but not RBWC pigeons, significant positive relationships were seen for aortic glycopeptide hexosamine and aortic cholesterol and for aortic glycopeptide hexose and aortic cholesterol. The findings implicate a possible role of aortic glycoproteins in either the initiation or modulation of atherosclerosis of the WC-2 pigeon.

Animals