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PubMed2006

Deconstructing mammalian reproduction: using knockouts to define fertility pathways.

Reproduction is the sine qua non for the propagation of species and continuation of life. It is a complex biological process that is regulated by multiple factors during the reproductive life of an organism. Over the past decade, the molecular mechanisms regulating reproduction in mammals have been rapidly unraveled by the study of a vast number of mouse gene knockouts with impaired fertility. The use of reverse genetics to generate null mutants in mice through targeted disruption of specific genes has enabled researchers to identify essential regulators of spermatogenesis and oogenesis in vivo and model human disorders affecting reproduction. This review focuses on the merits, utility, and the variations of the knockout technology in studies of reproduction in mammals.

Animals↗

PubMed2005

What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice?

A number of biochemical and physiological studies elucidated the roles of pituitary and placental glycoprotein hormones. Advances in the past two decades in manipulating the mouse genome by random or site-specific mutagenesis have heralded a new dimension to our understanding of the biology of gonadotropins. It is now possible to model many human reproductive disorders involving gonadotropins/gonadotropin-signaling in the mouse. Mutant mice selectively lacking either FSH or LH or their cognate receptors have been generated. The gonadotropin ligand and the corresponding receptor knockout mice mostly phenocopy each other. Analyses with these genetic models confirmed earlier physiological studies; in addition they also revealed novel roles for gonadotropins previously unrecognized. While FSH action seems dispensable for male but not female fertility, absence of LH causes infertility in both the sexes. While Sertoli cell number and germ cell carrying capacity of the Sertoli cells in compromised in FSH mutants, both somatic and germ cell lineages are affected in the LH mutants resulting in complete male infertility. FSH mutant females demonstrate a preantral stage block in folliculogenesis and FSH alone is not sufficient to promote full folliculogenesis in the absence of LH. Pre-ovulatory stage follicles do not form and most of the follicles undergo apoptosis in the absence of LH. Many extra-gonadal phenotypes have been described for the receptor knockout mice and whether these bear any resemblances to those in patients with similar inactivating mutations in the receptors for FSH and LH remains an open question. Thus the in vivo models will continue to have a significant impact in understanding gonadotropin physiology and pathophysiology and serve as novel genetic tools to study signaling mechanisms in the gonads.

Animals↗

PubMed2000

Cytokine expression and specific lymphocyte proliferation in two strains of Cryptosporidium parvum-infected gamma-interferon knockout mice.

Differences in the immune response between 2 strains of interferon-gamma knockout mice (BALB/c-GKO and C57BL/6-GKO) infected with Cryptosporidium parvum were examined because the course of infection among these 2 strains is markedly different. Infection of the BALB/c-GKO with C. parvum (2 X 10(6) oocysts/mouse) resulted in slight weight loss, oocyst shedding, and recovery from infection by 2 wk postinfection (PI). Infection with 100 oocysts in the C57BL/6-GKO mice resulted in significant weight loss, oocyst shedding, and death by day 10 PI. Splenocytes from infected mice were able to proliferate in a dose-dependent manner to soluble C. parvum-sporozoite antigen (SAg). In vitro stimulation with SAg resulted in an increase in interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor-alpha mRNA cytokine expression from splenocytes of infected BALB/cGKO mice. In contrast, only IL-5 mRNA expression was increased in the splenocytes from C. parvum-infected C57BL/6-GKO mice. Phenotypic analysis indicated no significant differences in the splenic cell populations. Previous studies indicated that susceptibility to C. parvum is dependent on CD4+ T cells and interferon-gamma production. The present study indicates that although both of these strains of knockout mice become infected with C. parvum, resolution of infection may be in part dependent on the expression of Th2 cytokines.

Animals↗

PubMed2002

Down but not out? A novel protein isoform of the estrogen receptor alpha is expressed in the estrogen receptor alpha knockout mouse.

The mouse knockout of the estrogen receptor alpha (ERalpha) gene, known as alphaERKO, has been extensively used for several years to study the role and function of ERalpha. Residual estradiol binding capacity in uterine tissue of 5-10% raised doubts if this knockout is a genuine null mutation of ERalpha. Although alternatively spliced ERalpha mRNA variants in the alphaERKO mouse were reported previously, the corresponding protein isoforms have not been detected to date. Here we show that a variant ERalpha protein, 61 kDa in size, is expressed in the uterine tissue of alphaERKO mice as a result of an alternative splicing. The transactivation capability of this protein is cell dependent and can be as high as 75% of the wild type ERalpha.

3T3 Cells↗

PubMed2004

Uremia accelerates both atherosclerosis and arterial calcification in apolipoprotein E knockout mice.

Chronic renal failure (CRF) favors the development of atherosclerosis and excessive calcification of atheromatous lesions. CRF was induced in apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3) factors involved in the calcification process. For creating CRF, 8-wk-old apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney ablation. Control animals underwent sham operation. Aortic atherosclerotic plaques and calcification were evaluated using quantitative morphologic image processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum urea, cholesterol, and triglyceride concentrations than non-CRF controls. The serum levels of advanced oxidation protein products were elevated in the uremic group and were correlated with serum urea levels. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. The relative proportion of calcified area to total surface area of both atherosclerotic lesions and lesion-free vascular tissue was increased in aortic root of uremic apoE(-/-) mice when compared with controls. The calcium deposits were made of hydroxyapatite and calcite crystals. In addition, plaques from uremic animals showed a significant increase in collagen content, whereas the degree of macrophage infiltration was comparable in both groups. There was no difference in mean arterial BP. These findings demonstrate that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances arterial calcification at both atheromatous intimal sites and atheroma-free medial sites. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia.

Animals↗

PubMed2005

Chloride transport in the kidney: lessons from human disease and knockout mice.

Knockout mouse models and human inherited diseases have provided important new insights into the physiologic role of chloride transport by CLC Cl(-) channels and KCC K-Cl co-transporters. ClC-K/barrtin Cl(-) channels are important for renal salt reabsorption and possibly for acid secretion by intercalated cells. The endosomal ClC-5 protein is crucial for proximal tubular endocytosis. Its disruption in mice and patients with Dent's disease leads to hypercalciuria and kidney stones through a pathologic cascade that may be entirely explained by an impairment of endocytosis. KCC4 is important for recycling Cl(-) for the basolateral anion exchanger in intercalated cells, as is evident from the renal tubular acidosis resulting from its knockout. Finally, both KCC3 and KCC4 are crucial for proximal tubular cell volume regulation.

Animals↗

PubMed2002

Angiotensin III activates nuclear transcription factor-kappaB in cultured mesangial cells mainly via AT(2) receptors: studies with AT(1) receptor-knockout mice.

Nuclear factor-kappaB (NF-kappaB) regulates many genes involved in renal pathophysiologic processes. It was previously demonstrated that angiotensin II (AngII) and its amino-terminal degradation product AngIII activate NF-kappaB in mesangial cells. However, which are the Ang receptor subtypes involved in the NF-kappaB pathway and whether these Ang peptides act through the same or different receptors in mesangial cells have not been evaluated. Under the culture conditions used, quiescent rat mesangial cells expressed both AT(1) and AT(2) receptors. To investigate the receptors involved in the NF-kappaB pathway, two different approaches were used, i.e., pharmacologic studies, using specific AT(1) and AT(2) receptor antagonists and agonists, and studies in AT(1) receptor-knockout mice. In cultured rat mesangial cells, both AT(1) and AT(2) receptor antagonists inhibited AngII-induced NF-kappaB DNA binding activity, whereas NF-kappaB activation elicited by AngIII was mainly blocked by the AT(2) receptor antagonist. Similar results were observed for cytosolic IkappaBalpha degradation. An AT(2) receptor agonist also activated NF-kappaB. In AT(1) receptor-knockout murine mesangial cells, AngIII and AngII increased NF-kappaB activity and degraded cytosolic IkappaBalpha; both processes were blocked by the AT(2) receptor antagonist. These data demonstrate that, in mesangial cells, NF-kappaB activation is mediated by AT(1) and AT(2) receptors, suggesting a novel intracellular signaling mechanism for AT(2) receptors in the kidney. Some differences in Ang peptide receptor-mediated responses were also observed. AngII activates NF-kappaB via AT(1) and AT(2) receptors, whereas AngIII acts mainly via AT(2) receptors. These results suggest the potential involvement of the AngIII/AT(2) receptor/NF-kappaB pathway in pathophysiologic processes in the kidney and provide a better understanding of the renin-angiotensin system.

Angiotensin III↗

PubMed2002

Mutational analysis of the serotonergic system: recent findings using knockout mice.

Serotonin modulates numerous processes in the central nervous system related to anxiety and fear, mood, aggression, sleep, ingestive behaviors, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several neuropsychiatric conditions but efforts to develop more specific pharmacological agents have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of serotonin as well as several enzymes that control its synthesis and metabolism but very few pharmacological agents are able to selectively target a single receptor. Several groups including ours have used a genetic strategy to ablate specific serotonin receptors in an effort to dissect out their functions in the central nervous system. The strength of this approach is the high degree of specificity that can be achieved in the knockout (gene inactivation) approach since a single receptor gene can be selectively targeted. To date several inactivation mutations of specific serotonin receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases knockout mice have been able to confirm what has already been suspected based on pharmacological studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior. In this review, the current literature regarding phenotypic changes in mice bearing inactivation mutations of serotonin receptors, the serotonin transporter, and the monoamine oxidase A will be discussed and major findings emphasized.

Animals↗

PubMed2000

Adipocyte metabolism in adipocyte fatty acid binding protein knockout mice (aP2-/-) after short-term high-fat feeding: functional compensation by the keratinocyte [correction of keritinocyte] fatty acid binding protein.

Mice null for adipocyte fatty acid binding protein (AFABP) compensate by increasing expression of keratinocyte fatty acid binding protein (KFABP) (Hotamisligil et al. Science 274:1377-1379, 1996). In the present study, AFABP knockout (KO) and wild-type (WT) mice became equally obese on a high-fat diet, as judged by fat pad weights, adipocyte size, and body composition analysis. High-fat feeding led to moderate insulin resistance in both WT and AFABP knockout mice, as indicated by an approximately 2-fold increase in plasma insulin. However, in the high fat-fed mice, plasma glucose levels were approximately 15% lower in the AFABP-KO mice. Adipocytes isolated from AFABP-KO and WT mice fed high- or low-fat diets exhibited similar rates of basal and norepinephrine-stimulated lipolysis and insulin-stimulated rates of glucose conversion to fatty acids and glyceride-glycerol. However, basal glucose conversion to fatty acids was higher in adipocytes of AFABP-KO mice. Adipocyte tumor necrosis factor-alpha release was similarly increased by high-fat diet-induced obesity in both WT and AFABP-KO mice. As assessed by Western blot analysis, the level of KFABP protein in AFABP-KOs was approximately 40% of the level of AFABP in WT controls. The binding affinities of KFABP for long-chain fatty acids were 2- to 4-fold higher than those of AFABP, but the relative affinities for different fatty acids were similar. As for AFABP, the rate of fatty acid transfer from KFABP to model phospholipid vesicles was increased with acceptor membrane concentration and by inclusion of acidic phospholipids, indicating a similar mechanism of transfer. We conclude KFABP can functionally compensate for the absence of AFABP, resulting in no major alterations in adipocyte metabolism or fat accumulation in response to short-term feeding of high-fat diets that result in moderate hyperinsulinemia.

Adaptation, Physiological↗

PubMed2004

Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived incretins that potentiate glucose clearance following nutrient ingestion. Elimination of incretin receptor action in GIPR(-/-) or GLP-1R(-/-) mice produces only modest impairment in glucose homeostasis, perhaps due to compensatory upregulation of the remaining incretin. We have now studied glucose homeostasis in double incretin receptor knockout (DIRKO) mice. DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4. Plasma glucagon and the hypoglycemic response to exogenous insulin were normal in DIRKO mice. Glycemic excursion was abnormally increased and levels of glucose-stimulated insulin secretion were decreased following oral but not intraperitoneal glucose challenge in DIRKO compared with GIPR(-/-) or GLP-1R(-/-) mice. Similarly, glucose-stimulated insulin secretion and the response to forskolin were well preserved in perifused DIRKO islets. Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin in wild-type and single incretin receptor knockout mice, the glucose-lowering actions of DPP-IV inhibitors were eliminated in DIRKO mice. These findings demonstrate that glucose-stimulated insulin secretion is maintained despite complete absence of both incretin receptors, and they delineate a critical role for incretin receptors as essential downstream targets for the acute glucoregulatory actions of DPP-IV inhibitors.

Animals↗

PubMed1997

Impact of knockout mice in toxicology.

Knockout mice obtained by homologous recombination technology may be valuable tools for in vivo investigations in toxicopathogenesis. A short review is given on the phenotype of mice with distinct deletions of cytokines and related genes. The application of these mice in pharmacological and toxicological research is discussed, with emphasis in endotoxic shock, hepatic toxicity, and myelotoxicity. The use of such knockout mice will be valuable for mechanistic studies in toxicology.

Acute-Phase Proteins↗

PubMed2003

p27Kip1 inactivation provides a proliferative advantage to transplanted hepatocytes in DPPIV/Rag2 double knockout mice after repeated host liver injury.

Studies were conducted to develop a new DPPIV(-/-)/Rag2(-/-) mouse model for hepatocyte transplantation by allogeneic and xenogeneic cells and to compare the proliferative capacity of p27 null hepatocytes versus normal hepatocytes in this system. Dipeptidyl peptidase IV (DPPIV) gene knockout mice, in which wild-type (wt) DPPIV+ donor hepatocytes can be readily identified by enzyme histochemistry, were bred with Rag2 null mice to prepare immunotolerant DPPIV(-/-)/Rag2(-/-) double knockout mice. DPPIV(-/-)/Rag(-/-) mice were transplanted with wt hepatocytes or p27 null mouse hepatocytes, which show enhanced cell cycle activity due to disruption of the Kip1 cyclin kinase inhibitor gene, and liver repopulation was assessed under nonproliferative versus proliferative experimental conditions. After their initial engraftment, transplanted wt hepatocytes did not proliferate in untreated livers or increase significantly in response to an acute liver regenerative stimulus. p27 null hepatocytes engrafted with the same efficiency as wt hepatocytes, but showed a noticeable, although not statistically significant, increase in proliferation in response to partial hepatectomy or acute CCl4 administration. Repeated treatments with CCl4 substantially increased proliferation and liver repopulation by p27 null hepatocytes but not by wt hepatocytes. These results suggest that p27 gene inactivation does not overcome proliferative restrictions imposed on hepatocytes by the normal liver, but that after repeated episodes of toxic liver injury, the augmented proliferative capacity of p27 null hepatocytes leads to significant liver repopulation compared with wt hepatocytes. These properties of p27-deficient hepatocytes could prove useful as a target for liver repopulation in patients with intermittent or a low level of chronic liver injury.

Animals↗

PubMed2005

Enhanced plasma ghrelin levels in Helicobacter pylori-colonized, interleukin-1-receptor type 1-homozygous knockout (IL-1R1-/-) mice.

AIM: Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor, and it plays a role in stimulating the growth hormone secretion, food intake, body weight gain and gastric motility. Eradication of Helicobacter pylori (H pylori) was shown to be associated with increase of the body weight. On the other hand, H pylori infection evokes the release of gastric IL-1beta. The present study was designed to investigate the involvement of the gastric IL-1 signal in the ghrelin dynamics in H pylori-colonized mice. METHODS: Twelve-week-old female IL-1-receptor type 1-homozygous-knockout mice (IL-1R1(-/-)) and their wild-type littermates (WT) were orally inoculated with H pylori (Hp group), while other cohorts received oral inoculation of culture medium (Cont group). Thirteen weeks after the inoculation, the mice were examined. The plasma and stomach ghrelin levels and the gastric preproghrelin mRNA were measured. RESULTS: Although the WT mice with H pylori infection showed a significantly decreased body weight as compared with that of the animals without H pylori infection, H pylori infection did not influence the body weight of the IL-1R1-knockout (IL-1R1(-/-)) mice. In the H pylori-infected IL-1R1(-/-) mice, the total and active ghrelin levels in the plasma were significantly increased, and the gastric ghrelin level was decreased. No significant differences were noted in the gastric preproghrelin mRNA expression. CONCLUSION: Ghrelin secretion triggered by H pylori infection might be suppressed by IL-1beta, the release of which is also induced by the infection, resulting in the body weight loss of mice with H pylori infection.

Animals↗

PubMed2000

Signal joint formation is also impaired in DNA-dependent protein kinase catalytic subunit knockout cells.

The effort to elucidate the mechanism of V(D)J recombination has given rise to a dispute as to whether DNA-dependent protein kinase catalytic subunit (DNA-PKcs) contributes to signal joint formation (sjf). Observations reported to date are confusing. Analyses using DNA-PKcs-deficient cells could not conclude the requirement of DNA-PKcs for sjf, because sjf can be formed by end-joining activities which are diverse among cells other than those participating in V(D)J recombination. Here, we observed V(D)J recombination in DNA-PKcs knockout cells and showed that both signal and coding joint formation were clearly impaired in the cells. Subsequently, to directly demonstrate the requirement of DNA-PKcs for sjf, we introduced full-length cDNA of DNA-PKcs into the knockout cells. Furthermore, several mutant DNA-PKcs cDNA constructs designed from mutant cell lines (irs-20, V3, murine scid, and SX9) were also introduced into the cells to obtain further evidence indicating the involvement of DNA-PKcs in sjf. We found as a result that the full-length cDNA complemented the aberrant sjf and that the mutant cDNAs constructs also partially complemented it. Lastly, we looked at whether the kinase activity of DNA-PKcs is necessary for sjf and, as a result, demonstrated a close relationship between them. Our observations clearly indicate that the DNA-PKcs controls not only coding joint formation but also the sjf in V(D)J recombination through its kinase activity.

Animals↗

PubMed2001

Studies using leukemia inhibitory factor (LIF) knockout mice and a LIF adenoviral vector demonstrate a key anti-inflammatory role for this cytokine in cutaneous inflammation.

Previous work has implicated the cytokine leukemia inhibitory factor (LIF) in cutaneous inflammation, although results have differed as to whether LIF is pro- or anti-inflammatory in this setting. We examined edema, inflammatory cell infiltration, and cytokine responses following CFA injection in the adult mouse footpad. Inflammatory cell infiltration and edema are significantly enhanced when CFA is injected in LIF knockout mice as compared with injection of wild-type littermates. Moreover, local injection of an adenoviral vector encoding LIF suppresses both measures of inflammation. In contrast, injection of an adenoviral vector encoding beta-galactosidase has no discernable effect on inflammation. In addition, comparison of the CFA responses in LIF knockout vs wild-type skin reveals that LIF is an important regulator of IL-1beta, IL-6, IL-7, IL-2Ralpha, and IFN-gamma in cutaneous inflammation. These and our previous data indicate that both endogenous and exogenous LIF are anti-inflammatory in the CFA model and that LIF is a key regulator of the cytokine cascade. The results also indicate that adenoviral gene delivery can be an effective therapeutic approach in this paradigm.

Adenoviridae↗

PubMed2003

TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells.

We have recently shown that effector T cells (T(E)) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, T(E) deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T(E) mediated complete tumor regression and cured wild-type animals with established pulmonary metastases of the B16BL6-D5 (D5) melanoma cell line. PKO/GKO T(E) also mediated tumor regression in D5 tumor-bearing PKO, GKO, or PKO/GKO recipients, although in PKO/GKO recipients efficacy was reduced. PKO/GKO T(E) exhibited tumor-specific TNF-alpha production and cytotoxicity in a 24-h assay, which was blocked by the soluble TNFRII-human IgG fusion protein (TNFRII:Fc). Blocking TNF in vivo by administering soluble TNFR II fusion protein (TNFRII:Fc) significantly reduced the therapeutic efficacy of PKO/GKO, but not wild-type T(E). This study identifies perforin, IFN-gamma, and TNF as a critical triad of effector molecules that characterize therapeutic antitumor T cells. These insights could be used to monitor and potentially tune the immune response to cancer vaccines.

Adoptive Transfer↗

PubMed2000

Exploitation of gene knockout mice models to study the pathogenesis of leprosy.

Shepard's technique for growth of Mycobacterium leprae in the mouse footpad, described in 1960, and more recent studies in thymectomized-irradiated mice and rats, athymic nude mice, nude rats and severe combined immunodeficiency (SCID) mice have defined the role of T-cell mediated immunity (CMI) in leprosy. However, the normal mouse and the immunocompromised mouse and rat represent only elements of polar tuberculoid disease and polar lepromatous leprosy, respectively. Transgenic, knockout (KO) mice may be employed to study the roles of individual genes in the ability of the host to mount an effective immune response to pathogens, and may also allow development of mouse models for the immunologically unstable borderline areas of the spectrum. We are exploiting certain KO mice to improve our understanding of CMI to M. leprae, and to study the role of the microenvironment of the leprosy granuloma in pathogenesis. CGD (chronic granulomatous disease) mice and iNOS-KO mice lack the ability to produce reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), respectively, whereas the T cells of GKO mice are unable to produce interferon-gamma (IFN gamma). iNOS-KO mice exhibit an enhanced capacity to form granulomas, and the histopathology of the infected footpad tissues of this strain share many elements of borderline tuberculoid disease. The macrophages of CGD mouse kill or inhibit multiplication of M. leprae, although they lack ROI. Multiplication of the organisms in the footpad is enhanced in GKO mice, although these mice retain some host resistance. In addition, we have been investigating supplementary, conditional approaches to KO mouse models. For example, the down-regulatory effects of local prostaglandin production can be controlled with essential fatty acid deficient diets or indomethacin, RNI can be blocked in CGD and GKO mice by treatment with aminoguanidine, NG monomethyl arginine or N6-(1-iminoethyl)-L-lysine, and local elaboration of TNF alpha can be neutralized by anti-TNF alpha antibody or excess TNF alpha receptor. Other cytokines can be neutralized by antibody as well, broadening the range of conditional knockout models.

Animals↗

PubMed1999

Susceptibility of immunodeficient gene-knockout mice to urinary tract infection.

PURPOSE: Clinical and experimental evidence indicates that mucosal immunity to urinary tract infection involves B and T-cell functions. The present study was conducted to assess the susceptibility of immunocompetent and immunodeficient mice with genetically engineered deletions in T and B-cell functions to experimentally induced urinary tract infections (UTI) with Escherichia coli. MATERIALS AND METHODS: Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10, inducible nitric oxide synthase, T cell receptor (TCR) delta-chain and JHD B cell-deficient gene knockout mice and their immunocompetent controls were challenged with uropathogenic Escherichia coli. The bladders and kidneys were cultured for viable E. coli at time intervals after intraurethral challenge to assess susceptibility to an experimentally induced UTI. RESULTS: Knockout mice with gammadelta-T cell or IFN-gamma deficiencies were more susceptible to UTI than immunocompetent mice or mice with immunodeficiencies in IL-10, IL-4, inducible nitric oxide synthase or antibody production (JHD). CONCLUSIONS: These data support an important role for gammadelta-T cells and IFN-gamma in resistance to UTI in mice.

Animals↗