Reduced Prostasin (CAP1/PRSS8) Activity Eliminates HAI-1 and HAI-2 Deficiency-Associated Developmental Defects by Preventing Matriptase Activation.

Loss of either hepatocyte growth factor activator inhibitor (HAI)-1 or -2 is associated with embryonic lethality in mice, which can be rescued by the simultaneous inactivation of the membrane-anchored serine protease, matriptase, thereby demonstrating that a matriptase-dependent proteolytic pathway is a critical developmental target for both protease inhibitors. Here, we performed a genetic epistasis analysis to identify additional components of this pathway by generating mice with combined deficiency in either HAI-1 or HAI-2, along with genes encoding developmentally co-expressed candidate matriptase targets, and screening for the rescue of embryonic development. Hypomorphic mutations in Prss8, encoding the GPI-anchored serine protease, prostasin (CAP1, PRSS8), restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos. Inactivation of genes encoding c-Met, protease-activated receptor-2 (PAR-2), or the epithelial sodium channel (ENaC) alpha subunit all failed to rescue embryonic lethality, suggesting that deregulated matriptase-prostasin activity causes developmental failure independent of aberrant c-Met and PAR-2 signaling or impaired epithelial sodium transport. Furthermore, phenotypic analysis of PAR-1 and matriptase double-deficient embryos suggests that the protease may not be critical for focal proteolytic activation of PAR-2 during neural tube closure. Paradoxically, although matriptase auto-activates and is a well-established upstream epidermal activator of prostasin, biochemical analysis of matriptase- and prostasin-deficient placental tissues revealed a requirement of prostasin for conversion of the matriptase zymogen to active matriptase, whereas prostasin zymogen activation was matriptase-independent.

Prevalence of caries and developmental defects of enamel in 9-10 year old children living in areas in Brazil differing water fluoride histories

Aims To assess the prevalences of caries, of developmental defects of enamel and their interrelationship in Brazilian 9-10-year-olds from areas of contrasting fluoridation histories.Methods systematic random sampling procedures were used to select children from an area where water had been fluoridated in 1963 and from a second area where water had been fluoridated since 1998. Clinical examinations for caries were carried out using the DMFT index and WHO diagnostic criteria. Developmental defects of enamel on upper incisors were diagnosed using the DDE index.Results A difference of 40% in DMFT was observed, with a lower prevalence of disease in the area fluoridated since 1963. Diffuse opacities affected 14.3% of the children from the area fluoridated since 1963 compared with only 2.4% in the area fluoridated in 1998. Children living in the area fluoridated in 1963 who had diffuse defects had twice the chance of being free from caries compared with those living in the same area who had no defects or who had only demarcated or hypoplastic defects.Conclusions This study confirms previous ones in showing the benefits of water fluoridation. Diffuse opacities of upper incisors affected relatively few subjects in either of the two areas.

Tissue-specific Expression of Dominant Negative Mutant Drosophila HSC70 Causes Developmental Defects and Lethality

The Drosophila melanogaster HSC3 and HSC4 genes encode Hsc70 proteins homologous to the mammalian endoplasmic reticulum (ER) protein BiP and the cytoplasmic clathrin uncoating ATPase, respectively. These proteins possess ATP binding/hydrolysis activities that mediate their ability to aid in protein folding by coordinating the sequential binding and release of misfolded proteins. To investigate the roles of HSC3 (Hsc3p) and HSC4 (Hsc4p) proteins during development, GAL4-targeted gene expression was used to analyze the effects of producing dominant negatively acting Hsc3p (D231S, K97S) and Hsc4p (D206S, K71S) proteins, containing single amino acid substitutions in their ATP-binding domains, in specific tissues of Drosophila throughout development. We show that the production of each mutant protein results in lethality over a range of developmental stages, depending on the levels of protein produced and which tissues are targeted. We demonstrate that the functions of both Hsc3p and Hsc4p are required for proper tissue establishment and maintenance. Production of mutant Hsc4p, but not Hsc3p, results in induction of the stress-inducible Hsp70 at normal temperatures. Evidence is presented that lethality is caused by tissue-specific defects that result from a global accumulation of misfolded protein caused by lack of functional Hsc70. We show that both mutant Hsc3ps are defective in ATP-induced substrate release, although Hsc3p(D231S) does undergo an ATP-induced conformational change. We believe that the amino acid substitutions in Hsc3p interfere with the structural coupling of ATP binding to substrate release, and this defect is the basis for the mutant proteins’ dominant negative effects in vivo.

Mutations in the small subunit of the Drosophila U2AF splicing factor cause lethality and developmental defects.

The essential eukaryotic pre-mRNA splicing factor U2AF (U2 small nuclear ribonucleoprotein auxiliary factor) is required to specify the 3' splice at an early step in spliceosome assembly. U2AF binds site-specifically to the intron polypyrimidine tract and recruits U2 small nuclear ribonucleoprotein to the branch site. Human U2AF (hU2AF) is a heterodimer composed of a large (hU2AF65) and small (hU2AF35) subunit. Although these proteins associate in a tight complex, the biochemical requirement for U2AF activity can be satisfied solely by the large subunit. The requirement for the small subunit in splicing has remained enigmatic. No biochemical activity has been found for hU2AF35 and it has been implicated in splicing only indirectly by its interaction with known splicing factors. In the absence of a biochemical assay, we have taken a genetic approach to investigate the function of the small subunit in the fruit fly Drosophila melanogaster. A cDNA clone encoding the small subunit of Drosophila U2AF (dU2AF38) has been isolated and sequenced. The dU2AF38 protein is highly homologous to hU2AF35 containing a conserved central arginine- and serine-rich (RS) domain. A recessive P-element insertion mutation affecting dU2AF38 causes a reduction in viability and fertility and morphological bristle defects. Consistent with a general role in splicing, a null allele of dU2AF38 is fully penetrant recessive lethal, like null alleles of the Drosophila U2AF large subunit.

Color masking of developmental enamel defects: a case series

Developmental defects involving color alteration of enamel frequently compromise the esthetic appearance of the tooth. The resin infiltration technique represents an alternative treatment for color masking of these lesions and uniformization of tooth color. This technique is considered relatively simple and microinvasive, since only a minimal portion of enamel is removed. This article illustrates the color-masking effect with resin infiltration of fluorosis and traumatic hypomineralization lesions with a case series. The final esthetic outcomes demonstrated the ability of the resin infiltrant to mask the color of white developmental defect lesions, resulting in satisfactory clinical esthetic improvements. However, in more severe cases, the color-masking effect was not complete.

Enamel Defects in Maxillary Central Incisors of Infants With Unilateral Cleft Lip

Objective: To evaluate the presence of enamel alterations in deciduous maxillary central incisors of infants with unilateral cleft lip and alveolar ridge, with or without cleft palate, and to compare the occurrence and location of these alterations between the central incisor adjacent to the cleft and the contralateral incisor. Design: Intraoral clinical examination was performed after tooth cleaning and drying by a single examiner with the aid of a dental mirror, dental probe, and artificial light, with the child positioned on a dental chair. The defects were recorded in a standardized manner according to the criteria of the Modified Developmental Defects of Enamel Index. Setting: Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) at Bauru, Sao Paulo, Brazil. Patients: One hundred one infants were evaluated. All were white, of both genders, aged 12 to 36 months and had at least two thirds of the crowns of maxillary incisors erupted. Results: Demarcated opacity was the most common defect at both cleft and noncleft sides, followed by diffuse opacity. The occurrence of hypoplasia at the cleft side was 11.8%. Most defects affected less than one third of the crown. Conclusion: The occurrence of enamel defects in deciduous maxillary central incisors of patients with unilateral cleft lip was 42.6%, mainly affecting the cleft side as to both number and severity.

Enamel Defects in Maxillary Central Incisors of Infants With Unilateral Cleft Lip

Objective: To evaluate the presence of enamel alterations in deciduous maxillary central incisors of infants with unilateral cleft lip and alveolar ridge, with or without cleft palate, and to compare the occurrence and location of these alterations between the central incisor adjacent to the cleft and the contralateral incisor.Design: Intraoral clinical examination was performed after tooth cleaning and drying by a single examiner with the aid of a dental mirror, dental probe, and artificial light, with the child positioned on a dental chair. The defects were recorded in a standardized manner according to the criteria of the Modified Developmental Defects of Enamel Index.Setting: Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) at Bauru, São Paulo, Brazil.Patients: One hundred one infants were evaluated. All were white, of both genders, aged 12 to 36 months and had at least two thirds of the crowns of maxillary incisors erupted.Results: Demarcated opacity was the most common defect at both cleft and noncleft sides, followed by diffuse opacity. The occurrence of hypoplasia at the cleft side was 11.8%. Most defects affected less than one third of the crown.Conclusion: The occurrence of enamel defects in deciduous maxillary central incisors of patients with unilateral cleft lip was 42.6%, mainly affecting the cleft side as to both number and severity.

Treatment of developmental defect of upper lip with carbon dioxide laser radiation (CO2): First surgical time

With the exception of the cleft lip, developmental defects (DD) of the lip are rare. The upper lip originates from the ectomesenchyme and is formed by the merging of the nasal medial and lateral processes with the maxillary process. Disturbances during this formation period can cause DD with functional and/or esthetic repercussions. We present a case of DD of the upper lip in a patient with a history of progressive growth of the left lateral portion of the upper lip that occurred from the time of birth until the age of 22 years. Clinical examination revealed hypertrophy of the area from the left philtral columns to the left commissure of the lip, extending the portion of the surface mucosa creating a flaccid and asymptomatic tissue mass. All other buccal structures appeared to be within normal limits and without any evidence of defects or deformities. In the surgical planning we decided to carry out corrective surgery in two phases. The first phase accomplished a conservative excision of the total abnormal labial tissue mass with a CO2 laser radiation (5 W in continuous mode, bunch diameter φ = 0.6 mm with a power density of 768 W/cm2 and fluency of 0.231 J/cm2) being careful to preserve the vermilion portion of the lip. Postsurgical clinical evaluations were done every three days until the skin sutures were removed and then every seven days until two months post surgery. While the entire mass of excessive tissue could not be completely removed, the removal of the excessive mucosal tissue produced a very good outcome relative to lip function, with a good esthetic result without scarring, and good tissue mobility. The results showed that the CO2 laser is an extremely useful instrument that can provide excellent control of the surgical field and allow for healing that produces excellent functional and esthetic results. © 2005 Taylor & Francis.

DEVELOPMENTAL AND CELLULAR FUNCTIONS OF DELTA-CATENIN

Catenins have diverse and powerful roles in embryogenesis, homeostasis or disease progression, as best exemplified by the well-known beta-catenin. The less studied delta-catenin likewise contains a central Armadillo-domain. In common with other p120 sub-class members, it acts in a variety of intracellular compartments and modulates cadherin stability, small GTPase activities and gene transcription. In mammals, delta-catenin exhibits neural specific expression, with its knock-out in mice correspondingly producing cognitive defects and synaptic dysfunctions. My work instead employed the amphibian, Xenopus laevis, to explore delta-catenin’s physiological functions in a distinct vertebrate system. Initial isolation and characterization indicated delta-catenin’s expression in Xenopus. Unlike the pattern observed for mammals, delta-catenin was detected in most adult Xenopus tissues, although enriched in embryonic structures of neural fate as visualized using RNA in-situ hybridization. To determine delta-catenin’s requirement in amphibian development, I employed anti-sense morpholinos to knock-down gene products, finding that delta-catenin depletion results in developmental defects in gastrulation, neural crest migration and kidney tubulogenesis, phenotypes that were specific based upon rescue experiments. In biochemical and cellular assays, delta-catenin knock-down reduced cadherin levels and cell adhesion, and impaired activation of RhoA and Rac1, small GTPases that regulate actin dynamics and morphogenetic movements. Indeed, exogenous C-cadherin, or dominant-negative RhoA or dominant-active Rac1, significantly rescued delta-catenin depletion. Thus, my results indicate delta-catenin’s essential roles in Xenopus development, with contributing functional links to cadherins and Rho family small G proteins. In examining delta-catenin’s nuclear roles, I identified delta-catenin as an interacting partner and substrate of the caspase-3 protease, which plays critical roles in apoptotic as well as non-apoptotic processes. Delta-catenin’s interaction with and sensitivity to caspase-3 was confirmed using assays involving its cleavage in vitro, as well as within Xenopus apoptotic extracts or mammalian cell lines. The cleavage site, a highly conserved caspase consensus motif (DELD) within Armadillo-repeat 6 of delta-catenin, was identified through peptide sequencing. Cleavage thus generates an amino- (1-816) and carboxyl-terminal (817-1314) fragment each containing about half of the central Armadillo-domain. I found that cleavage of delta-catenin both abolishes its association with cadherins, and impairs its ability to modulate small GTPases. Interestingly, the carboxyl-terminal fragment (817-1314) possesses a conserved putative nuclear localization signal that I found is needed to facilitate delta-catenin’s nuclear targeting. To probe for novel nuclear roles of delta-catenin, I performed yeast two-hybrid screening of a mouse brain cDNA library, resolving and then validating its interaction with an uncharacterized KRAB family zinc finger protein I named ZIFCAT. My results indicate that ZIFCAT is nuclear, and suggest that it may associate with DNA as a transcriptional repressor. I further determined that other p120 sub-class catenins are similarly cleaved by caspase-3, and likewise bind ZIFCAT. These findings potentially reveal a simple yet novel signaling pathway based upon caspase-3 cleavage of p120 sub-family members, facilitating the coordinate modulation of cadherins, small GTPases and nuclear functions. Together, my work suggested delta-catenin’s essential roles in Xenopus development, and has revealed its novel contributions to cell junctions (via cadherins), cytoskeleton (via small G proteins), and nucleus (via ZIFCAT). Future questions include the larger role and gene targets of delta-catenin in nucleus, and identification of upstream signaling events controlling delta-catenin’s activities in development or disease progression.

Knock-out of Arabidopsis metal transporter gene IRT1 results in iron deficiency accompanied by cell differentiation defects

IRT1 and IRT2 are members of the Arabidopsis ZIP metal transporter family that are specifically induced by iron deprivation in roots and act as heterologous suppressors of yeast mutations inhibiting iron and zinc uptake. Although IRT1 and IRT2 are thought to perform redundant functions as root-specific metal transporters, insertional inactivation of the IRT1 gene alone results in typical symptoms of iron deficiency causing severe leaf chlorosis and lethality in soil. The irt1 mutation is characterized by specific developmental defects, including a drastic reduction of chloroplast thylakoid stacking into grana and lack of palisade parenchyma differentiation in leaves, reduced number of vascular bundles in stems, and irregular patterns of enlarged endodermal and cortex cells in roots. Pulse labeling with 59Fe through the root system shows that the irt1 mutation reduces iron accumulation in the shoots. Short-term labeling with 65Zn reveals no alteration in spatial distribution of zinc, but indicates a lower level of zinc accumulation. In comparison to wild-type, the irt1 mutant responds to iron and zinc deprivation by altered expression of certain zinc and iron transporter genes, which results in the activation of ZIP1 in shoots, reduction of ZIP2 transcript levels in roots, and enhanced expression of IRT2 in roots. These data support the conclusion that IRT1 is an essential metal transporter required for proper development and regulation of iron and zinc homeostasis in Arabidopsis.

Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

Developmental anomalies of the eye: the genetic link

As in other areas of the body, developmental anomalies of the eye arise as a result of the disturbance of events during embryology and in a proportion of cases these anomalies are genetically inherited. Developmental anomalies that occur early in embryonic life may be so severe that the embryo may not survive but others result in the birth of healthy babies but with developmental eye defects of varying severity. The most dramatic developmental defects of the eye include anophthalmos (complete absence of an eye), microphthalmos (a general failure of the eye to develop resulting in a small, undeveloped eye), coloboma (caused by failure of the optic vesicle to invaginate), and aniridia (complete or partial loss of the iris). The present article does not provide an exhaustive review of the topic but considers the major types of developmental anomaly to affect the eye and will discuss how recent progress in genetics has increased our understanding of these disorders. The major genes linked to the developmental anomalies are discussed as well as how defects in these genes might lead to specific problems.

The P450 oxidoreductase, RedA, controls development beyond the mound stage in Dictyostelium discoideum

Background: NADPH-cytochrome- P450 oxidoreductase (CPR) is a ubiquitous enzyme that belongs to a family of diflavin oxidoreductases and is required for activity of the microsomal cytochrome-P450 monooxygenase system. CPR gene-disruption experiments have demonstrated that absence of this enzyme causes developmental defects both in mouse and insect. Results: Annotation of the sequenced genome of D. discoideum revealed the presence of three genes (redA, redB and redC) that encode putative members of the diflavin oxidoreductase protein family. redA transcripts are present during growth and early development but then decline, reaching undetectable levels after the mound stage. redB transcripts are present in the same levels during growth and development while redC expression was detected only in vegetative growing cells. We isolated a mutant strain of Dictyostelium discoideum following restriction enzyme-mediated integration (REMI) mutagenesis in which redA was disrupted. This mutant develops only to the mound stage and accumulates a bright yellow pigment. The mound-arrest phenotype is cell-autonomous suggesting that the defect occurs within the cells rather than in intercellular signaling. Conclusion: The developmental arrest due to disruption of redA implicates CPR in the metabolism of compounds that control cell differentiation.

Concentração de chumbo, defeitos de esmalte e cárie em dentes decíduos

OBJETIVO: Verificar a relação da concentração de chumbo no esmalte de dentes decíduos com a presença de defeitos de esmalte e sua relação com cárie dental em pré-escolares. MÉTODOS: A amostra foi de 329 crianças de pré-escolas municipais de uma área próxima de indústrias (N=132) e outra não industrial (N=197) da cidade de Piracicaba, Estado de São Paulo. Essa amostra pertencente a um estudo inicial realizado entre 2000 e 2001 no qual o chumbo foi analisado por meio de biópsia de esmalte. Foram realizados exames clínicos bucais para verificação da prevalência de defeitos de esmalte (Developmental Defects of Enamel Index - DDE, da Federação Dentária Internacional - FDI) e cárie (Índice ceos, Organização Mundial da Saúde), em ambas regiões. Foram utilizados teste de qui-quadrado e cálculo do risco relativo ao nível de significância de 5%, considerando cada região separadamente. RESULTADOS: Houve maior proporção de crianças com cárie entre aquelas com maiores concentrações de chumbo nos decíduos na região não industrial (p=0,02), o que não se observou na região industrial (p=0,89). Houve risco relativo (RR) aumentado de cárie nas crianças da região não industrial o que não foi verificado nas crianças da região industrial. Não se observou relação entre a presença de chumbo e os defeitos de esmalte. CONCLUSÕES: Não foram encontados dados que evidenciassem a relação entre concentração de chumbo e defeitos no esmalte em nenhuma das regiões pesquisadas. Não foi encontrada relação entre chumbo e cárie na região industrial, ressaltando a necessidade de mais estudos dessas relações.

Étude de la fonction de GLUT8 sur un modèle de souris "knock-out"

Résumé GLUT8 est la première des nouvelles isoformes des GLUT récemment identifiés. Il est fortement exprimé dans les testicules et plus faiblement dans les blastocystes, le cerveau, particulièrement au niveau de l'hippocampe, et le coeur. En conditions basales, il est retenu dans un compartiment intracellulaire. Si on l'exprime en surface cellulaire, par la mutation du motif d'internalisation dileucine, il transporte le glucose avec une bonne affinité. Dans le but d'étudier sa fonction au niveau de l'organisme, nous avons créé un modèle de knock out conditionnel, en entourant le dernier exon du gène de GLUT8 par deux sites loxP. En croisant nos souris avec une souche de souris transgénique exprimant la cre-recombinase dans les cellules de la lignée germinale, nous avons généré un modèle de souris portant la délétion totale de GLUT8 de manière constitutionnelle. Les statistiques effectuées sur les premières naissances indiquent qu'une partie des souris knock out ne survit pas, suggérant un rôle de GLUT8 au niveau du développement embryonnaire. Les souris qui ont survécu ne présentent toutefois pas d'anomalies durant la croissance et sont fertiles. Elles ont des taux de glucose et d'insuline sanguins normaux. Au niveau cérébral, la structure de l'hippocampe n'est pas modifiée par la suppression de GLUT8, cependant, les souris GLUT8-/- présentent une prolifération cellulaire augmentée dans le gyrus denté. Cette augmentation de division cellulaire pourrait être la réponse adaptée à une éventuelle augmentation de la mort cellulaire au niveau de l'hippocampe. Elles ne semblent toutefois pas présenter de défauts cognitifs majeurs dans le bassin de Morris en conditions normales. Toutefois, en conditions de jeûne, elles tendent à une meilleure mémorisation à court terme. Les études morphologiques et histologiques au niveau cardiaque n'ont pas révélé de d'hypertrophie au niveau ventriculaire. La stimulation de la contraction à l'isoprotérénol n'a pas mis en évidence de défaut d'adaptation des coeurs GLUT8-/-. Cependant l'analyse fonctionnelle par électrocardiogramme, en conditions basales, a montré une augmentation de la durée de l'onde P, suggérant un défaut dans la dépolarisation des oreillettes. Nos résultats indiquent que GLUT8 ne joue pas un rôle prédominant dans la survie et la fonction basale des souris. Il pourrait jouer un rôle plus important dans des situations stressantes pour l'organisme, comme l'hypoglycémie ou les conditions d'ischémie qui induiraient son expression à la membrane plasmique et stimuleraient le captage du glucose. Abstract GLUT8 was the first of the recently identified isoform of the GLUT family proteins. It is strongly expressed in the testis. It is also found at a lower level in the blastocyst, in heart and in the brain. Under basal conditions, it is retained in the intracellular compartment, but when the internalization motif dileucine is mutated, GLUT8 translocates to the plasma membrane and transports glucose with a relatively high affinity. To study its function in vivo, we created a conditional knock out mouse model. To do so, we targeted the last exon of the GLUT8 gene with two loxP sites. We then crossed these mice with a transgenic model expressing the cre-recombinase in the gem' line to generate a constitutional total knock out mouse. The statistics made on the first breedings showed that some of the knock out mice do not survive, suggesting a role of GLUT8 in the embryonic development. Conversely mice who survive do not show developmental defects and they are fertile with normal glucose and insulin blood levels. In the brain, the general structure of the hippocampus is not modified by the deletion of GLUT8. However, GLUT8-/- mice show an increase in the cell proliferation in the dentate gyms. This cell proliferation could be due to an increase in the cell death in the hippocampus. When tested in the morris water maze, these mice do not show any cognitive defects in the basal conditions, but they have a tendency to learn better in fasted conditions. The morphological and histological studies made at the heart level did not show any cardiac hypertrophy in the ventricles. The stimulation with isoproterenol did not show any adaptation defects in the GLUT8-/- hearts. However, the functional analysis made in basal conditions with the electrocardiogram showed an increase in the P wave length, suggesting a defect in the atrial depolarization in the knock out mice. Overall, our results show that GLUT8 does not play an important role in the basal general functions in the mice, but might play a more important role during whole organism stress. Hypoglycaemia or ischemia, for example could stimulate the GLUT8 translocation to the plasma membrane to increase specifically glucose uptake. Résumé tout public Les différentes cellules de l'organisme possèdent des propriétés particulières, qui leur permettent de maintenir les fonctions de l'organe auquel elles appartiennent. La membrane plasmique qui les délimite sélectionne les substances qui vont pénétrer à l'intérieur de la cellule et permet ainsi de maintenir un environnement interne constant. Le glucose est une source d'énergie importante pour la cellule et doit pouvoir pénétrer à l'intérieur de la cellule. Il utilise pour cela des protéines de transport qui le feront passer de part et d'autre de la membrane. Les protéines de la famille des GLUT (pour GLUcose Transporter) possèdent cette capacité. GLUT8 est un membre de la famille des GLUT identifié récemment. Il possède la capacité de transporter le glucose quand il se présente à la surface de la cellule. Il est principalement exprimé dans les testicules, dans le coeur et le cerveau et durant le développement embryonnaire. Son rôle n'est toutefois pas encore défini. Ce travail consiste à étudier la fonction de GLUT8 au niveau de l'organisme entier. Nous avons créé un modèle de souris dans lesquelles l'expression de GLUT8 a été supprimée pour mettre en évidence son importance dans le maintien de l'intégrité des fonctions du corps. Les observations effectuées sur les souris qui n'expriment plus GLUT8 nous indiquent que leurs cellules prolifèrent plus vite au niveau de l'hippocampe. L'hippocampe est une structure située dans le cerveau qui est impliquée dans les phénomènes d'apprentissage. Les souris qui ont été testées dans des tâches d'apprentissage n'ont malgré cela pas montré une amélioration de la mémorisation. Dans le coeur, la suppression de GLUT8 semble présenter un défaut quand on mesure l'activité électrique du coeur par électrocardiogramme. Toutefois, ils fonctionnent normalement et ne présentent pas de défauts morphologiques en conditions normales. Les expériences effectuées sur les modèles de souris indiquent que GLUT8 ne jouerait pas un rôle prédominant dans le fonctionnement normal du corps. Il pourrait exercer sa fonction dans des situations plus particulières comme l'hypoglycémie, où il permettrait une meilleure capacité à transporter le glucose dans les cellules.