Targeted Disruption of the Peptide Transporter <i>Pept2</i> Gene in Mice Defines Its Physiological Role in the Kidney

Rubio‐Aliaga, Isabel; Frey, Isabelle; Boll, Michael; Groneberg, David A.; Eichinger, H; Balling, Rudi; Daniel, Hannelore

doi:10.1128/mcb.23.9.3247-3252.2003

Cited by 97 publications

(83 citation statements)

References 30 publications

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“…However, with regard to the investigation of immunological mechanisms underlying the allergic eye disease, the guinea-pig models appear to be clearly limited as there are only restricted numbers of genetic and immunological data of the existing species and different strains. In addition, techniques such as gene depletion (57), gene arrays (58) or analysis of mRNA on a single cell level (59) are currently not possible because of missing genomic data.…”

Section: Guinea-pigsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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Numerous recent reports have demonstrated an increase in the prevalence and incidence of allergic conditions during the past years which affect approximately 25% of the general population (1) and about US$ 6 billion alone are estimated as direct costs of allergic rhinoconjunctivitis (2). Whereas a large amount of studies have focused on the pathophysiology of allergic rhinitis and asthma over the past years, ocular allergies are less well studied. However, allergic diseases affecting the eye are very common (3) and pediatric studies have shown that within distinct cohorts, up to 32% of allergic children have an ocular allergy as the primary manifestation of allergy (4). Allergic eye diseases such as allergic conjunctivitis commonly present with the symptoms of itchy, watery, red, sore and swollen eyes, but not pain (5).In contrast to the large amount of experimental studies on allergic asthma and the detailed knowledge that exists on mediators of allergic airway inflammation (6-8), there are few experimental studies using models of allergic eye diseases. Detailed reviews to assess the pathophysiology and immunology of ocular allergies have been limited. This review hopefully fills this void to provide the clinical and translational researcher in the area of ocular allergy. Pathophysiology of ocular allergiesBefore characterizing the different animal models of ocular allergy which have been established so far, it is crucial to reflect that within the area of ocular allergies, different disease entities exist and that only some of them may be mimicked by animal models. Formally, conjunctivitis may be divided into allergic and nonallergic conjunctivitis and the allergic form may also be subdivided into IgE-mediated and non-IgE-mediated allergic conjunctivitis ( Fig. 1) (9). Clinically, the spectrum of conjunctivitis types can be subdivided into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis and giant papillary conjunctivitis.In contrast to the other forms of conjunctivitis, allergic conjunctivitis is commonly based on an IgEmediated hypersensitivity reaction. Furthermore, allergic Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small numbe...

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Section: Guinea-pigsmentioning

confidence: 99%

Animal models of allergic and inflammatory conjunctivitis

Groneberg

Bielory

Fischer

et al. 2003

Allergy

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“…The recent generation of PEPT2 knockout mice by this laboratory (13) and by Rubio-Aliaga and coworkers (16) has provided a powerful tool to directly examine the physiologic and pharmacologic significance of PEPT2 in the transport of small peptides and peptidomimetics in multiple organ systems. Recent results have provided strong evidence that PEPT2 is the primary transporter for uptake of carnosine (␤-alanyl-L-histidine) and cefadroxil (aminocephalosporin) at the BCSFB (12,14).…”

Section: Introductionmentioning

confidence: 99%

Role of PEPT2 in the Choroid Plexus Uptake of Glycylsarcosine and 5-Aminolevulinic Acid: Studies in Wild-Type and Null Mice

Ocheltree

Shen

et al. 2004

Pharm Res

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Purpose. To determine the importance of PEPT2 in the uptake of glycylsarcosine (GlySar) and 5-aminolevulinic acid (5-ALA) in mouse choroid plexus whole tissue. Methods. Uptake studies were performed in bicarbonate artificial cerebrospinal fluid buffer using choroid plexuses isolated from PEPT2 +/+ and PEPT2 −/− mice. Results. PEPT2−/− mice exhibited a 90% reduction in GlySar uptake (p < 0.001) and a 92% reduction in 5-ALA uptake (p < 0.001) as compared to wild type animals. At 4°C (vs. 37°C), GlySar uptake was reduced by 95% in PEPT2 +/+ mice; no difference was observed in null animals. Unlabeled GlySar inhibited the uptake of [ ). Low sodium buffer (1 mM) resulted in 75% and 59% reductions, respectively, in GlySar (p < 0.001) and 5-ALA (p < 0.01) uptake in PEPT2 +/+ mice; no differences were observed in PEPT2 −/− mice. Overall, about 90-95% of the choroid plexus uptake of GlySar and 5-ALA was mediated by PEPT2, with about 5-10% of the residual uptake occurring by nonspecific mechanisms.Conclusions. The results demonstrate that PEPT2 is the only transporter responsible for the choroid plexus uptake of GlySar and 5-ALA. They also suggest a role for PEPT2 in the clearance of dipeptides and endogenous peptidomimetics from cerebrospinal fluid.

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“…However, experiments demonstrated that PEPT2-null animals were healthy and fertile. In addition, neither clinical chemistry data obtained from plasma and urine samples nor general physiological measures indicated any significant metabolic perturbation (4,20,21). Therefore, the exact physiological role of PEPT2 warrants further studies.…”

Section: Tmds 9 and 10 (16)mentioning

confidence: 99%