A comparison of molecular alterations in environmental and genetic rat models of ADHD: A pilot study

DasBanerjee, Tania; Middleton, Frank A.; Berger, David F.; Lombardo, John P.; Sagvolden, Terje; Faraone, Stephen V.

doi:10.1002/ajmg.b.30877

Cited by 69 publications

(70 citation statements)

References 58 publications

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“…However, dystonia rarely occurs among 18p deletion patient who are hemizygous for GNAL . GNAL also was a susceptible gene for ADHD with preferential transmission of maternal alleles [DasBanerjee et al, 2008;Laurin et al, 2008]. Although the patient in our study did not have dystonia, she did have manifestations of ADHD with a possible contribution of GNAL loss.…”

Section: Discussionmentioning

confidence: 46%

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

Sun

Wan²,

Wang³

et al. 2018

Cytogenet Genome Res

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18p deletion syndrome is a rare chromosomal disease caused by deletion of the short arm of chromosome 18. By using cytogenetic and SNP array analysis, we identified a girl with 18p deletion syndrome exhibiting craniofacial anomalies, intellectual disability, and short stature. G-banding analysis of metaphase cells revealed an abnormal karyotype 46,XX,del(18)(p10). Further, SNP array detected a 15.3-Mb deletion at 18p11.21p11.32 (chr18:12842-15375878) including 61 OMIM genes. Genotype-phenotype correlation analysis showed that clinical manifestations of the patient were correlated with LAMA1, TWSG1, and GNAL deletions. Her neuropsychological assessment test demonstrated delay in most cognitive functions including impaired mathematics, linguistic skills, visual motor perception, respond speed, and executive function. Meanwhile, her integrated visual and auditory continuous performance test (IVA-CPT) indicated a severe comprehensive attention deficit. At age 7 and 1/12 years, her height was 110.8 cm (-2.5 SD height for age). Growth hormone (GH) treatment was initiated. After 27 months treatment, her height was increased to 129.6 cm (-1.0 SD height for age) at 9 and 4/12 years, indicating an effective response to GH treatment.

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Section: Discussionmentioning

confidence: 46%

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

Sun

Wan²,

Wang³

et al. 2018

Cytogenet Genome Res

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“…Normotensive Wistar-Kyoto rats (WKY) are normally used as the control rats (1). Since SHR and SHRSP are not only used as rat models of essential hypertension and stroke, but also as rat models of attentiondeficit hyperactivity disorder (ADHD), studies using these rat models are expected to reveal genes not only related to hypertension and stroke, but also those related to ADHD (3)(4)(5)(6). In a previous study, as the first step of this project, we investigated gene expression profiles in adrenal glands in these 3 rats strains when the rats were 3 and 6 weeks of age (7).…”

Section: Introductionmentioning

confidence: 99%

Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the brain

Yoshida

Watanabe

Yamanishi

et al. 2014

International Journal of Molecular Medicine

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Abstract. Spontaneously hypertensive rats (SHR) and strokeprone SHR (SHRSP) are frequently used as rat models not only of essential hypertension and stroke, but also of attention-deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto rats (WKY) are used as the control rats in these cases. An increasing number of studies has demonstrated the critical role of the central nervous system in the development and maintenance of hypertension. In a previous study, we analyzed the gene expression profiles in the adrenal glands of SHR. Thus, in this study, we analyzed gene expression profiles in the brains of SHR in order to identify the genes responsible for causing hypertension and stroke, as well as those involved in ADHD. Using genome-wide microarray technology, we examined the gene expression profiles in the brains of 3 rat strains (SHR, SHRSP and WKY) when the rats were 3 and 6 weeks of age, a period in which the rats are considered to be in a prehypertensive state. Gene expression profiles in the brain were compared between SHR and WKY, and between SHRSP and SHR. A total of 179 genes showing a >4-or <-4-fold change in expression were isolated, and candidate genes were selected using two different web tools: the first tool was the Database for Annotation, Visualization and Integrated Discovery (DAVID), which was used to search for significantly enriched genes, and categorized them using Gene Ontology (GO) terms, and the second was the network explorer of Ingenuity Pathway Analysis (IPA), which was used to search for interaction networks among SHR-and SHRSP-specific genes. The IPA of SHR-specific genes revealed that prostaglandin E receptor 4 (Ptger4) is one of the candidate genes responsible for causing hypertension in SHR, and that albumin (Alb) and chymase 1 (Cma1) are also responsible for causing hypertension in SHR in the presence of angiotensinogen (Agt). Similar analyses of SHRSP-specific genes revealed that the angiotensin II receptorassociated gene (Agtrap) interacts with the FBJ osteosarcoma oncogene (Fos), and with the angiotensin II receptor type-1b (Agtr1b). As Agtrap and Agtr1b not only participate in the 'uptake of norepinephrine' and 'blood pressure', but also in the 'behavior' of SHRSP at 6 weeks of age, our data demonstrate a close association between hypertension and ADHD.

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“…In 2008, The STAR Consortium published the first whole genome-wide SNP data for 167 distinct inbred rat strains, including 13 SHR and 9 WKY inbred substrains and many other related congenic strains. During the same time, our group, in collaboration with Dr. Terje Sagvolden (1945Sagvolden ( -2011 from University of Oslo (Oslo, Norway), began to use Af-fymetrix genotyping arrays and gene expression arrays to examine the genetic differences of SHR and WKY substrains in order to understand variations in their ADHD-like behaviors (5,22,23,26). The observations of the complex and large genetic variations among these strains from these studies and the concerns raised due to their phenotypic heterogeneity prompted us to further analyze their genetic relationship.…”

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confidence: 99%

Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources

Zhang-James

Middleton

Faraone

2013

Physiological Genomics

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Zhang-James Y, Middleton FA, Faraone SV. Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources. Physiol Genomics 45: 528 -538, 2013. First published May 14, 2013 doi:10.1152/physiolgenomics.00002.2013.-The spontaneously hypertensive rat (SHR) has been widely used as a model for studies of hypertension and attention deficit/hyperactivity disorder. The inbred Wistar-Kyoto (WKY) rat, derived from the same ancestral outbred Wistar rat as the SHR, are normotensive and have been used as the closest genetic control for the SHR, although the WKY has also been used as a model for depression. Notably, however, substantial behavioral and genetic differences among the WKY substrains, usually from the different vendors and breeders, have been observed. These differences have often been overlooked in prior studies, leading to inconsistent and even contradictory findings. The complicated breeding history of the SHR and WKY rats and the lack of a comprehensive understanding of the genetic background of different commercial substrains make the selection of control rats a daunting task, even for researchers who are mindful of their genetic heterogeneity. In this study, we examined the genetic relationship of 16 commonly used WKY and SHR rat substrains using genome-wide SNP genotyping data. Our results confirmed a large genetic divergence and complex relationships among the SHR and WKY substrains. This understanding, although incomplete without the genome sequence, provides useful guidance in selecting substrains and helps to interpret previous reports when the source of the animals was known. Moreover, we found two closely related, yet distinct WKY substrains that may provide novel opportunities in modeling psychiatric disorders.WKY; SHR; autism; ADHD; inbred rat; animal models; SNP; behavior THE SPONTANEOUSLY HYPERTENSIVE rat (SHR) is an inbred strain established from outbred Wistar rats selected for high blood pressure (8a). Although the SHR develops hypertension spontaneously at the age of 7-15 wk (36), prior to this age they have been used and validated as a model for attention deficit/hyperactivity disorder (ADHD), demonstrating all three ADHD core symptoms: hyperactivity, impulsivity, and inattentiveness (25, 28). The Wistar-Kyoto (WKY) strain was established from the same parental Wistar stock as the SHR and as a result has been commonly used as a control strain for the SHR (8a). Notably, however, the sources of WKY rats often varies between studies, and significant variability in the comparative results that employed these substrains has been noted, probably because the WKY breeding stock was distributed to different breeders prior to being fully inbred (11,13,21). In addition, the littermate pairings that produced the inbred WKY from the Wistar rat were initiated Ͼ10 yr after the inbreeding for the SHR was initiated (13), thus increasing the heterogeneity between the WKY and SHR and leading some to question the validity of the WKY as a control strain for SHR (30). ...

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A comparison of molecular alterations in environmental and genetic rat models of ADHD: A pilot study

Cited by 69 publications

References 58 publications

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the brain

Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources

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