Displaying publications 1 - 20 of 73 in total

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  1. Jafarian S, Ling KH, Hassan Z, Perimal-Lewis L, Sulaiman MR, Perimal EK
    Alzheimers Dement (N Y), 2019;5:637-643.
    PMID: 31687471 DOI: 10.1016/j.trci.2019.09.009
    Introduction: We investigated the effects of zerumbone (1 and 10 mg/kg) against hyperactivity, anxiety and memory impairment in scopolamine-induced dementia in Sprague-Dawley rats.

    Methods: Open field tests, elevated plus maze and Morris water maze were performed to assess general locomotor activity, anxiety-like behaviours and learning and memory processes respectively in rats pretreated with scopolamine.

    Results: Scopolamine-treated rats showed high total activity, stereotype, and total distance travelled in the open field arena, reduced number of entries to open arms, decreased the percentage of time spent in open arms and higher escape latency time in the Morris water maze test. Interestingly, single administration of zerumbone (1 and 10 mg/kg) reversed the hyperactivity, anxiety-like behaviours, and learning impairment effects of scopolamine in the three experimental model studied respectively.

    Discussion: Our findings demonstrated that the scopolamine-induced impairment of learning and memory was reversed by the administration of zerumbone. As a conclusion, our findings presented the positive effects of zerumbone on dementia-like behaviours in the animal model used and could possibly contribute for future research to manage hyperactivity, anxiety, and learning disabilities.

  2. Say YH, Ling KH, Duraisamy G, Isaac S, Rosli R
    BMC Cardiovasc Disord, 2005;5(1):7.
    PMID: 15811183
    Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.
  3. Ling KH, Hewitt CA, Tan KL, Cheah PS, Vidyadaran S, Lai MI, et al.
    BMC Genomics, 2014;15:624.
    PMID: 25052193 DOI: 10.1186/1471-2164-15-624
    The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84.
  4. Zainal Abidin S, Tan EL, Chan SC, Jaafar A, Lee AX, Abd Hamid MH, et al.
    BMC Neurol, 2015;15:59.
    PMID: 25896831 DOI: 10.1186/s12883-015-0316-2
    Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis.
  5. Lee SS, Ling KH, Tusimin M, Subramaniam R, Rahim KF, Loh SP
    BMC Pregnancy Childbirth, 2020 Nov 23;20(1):714.
    PMID: 33228578 DOI: 10.1186/s12884-020-03397-7
    BACKGROUND: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.

    METHOD: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using a questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using an Ultra-High-Performance Liquid Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.

    RESULTS: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD

  6. Bala U, Tan KL, Ling KH, Cheah PS
    BMC Res Notes, 2014;7:714.
    PMID: 25304607 DOI: 10.1186/1756-0500-7-714
    Over the past several decades, many studies concerning peripheral nerve damage or regeneration have been performed. Mice have been widely used for many of these studies, with the sciatic nerve being the most targeted and preferred nerve. Therefore, techniques for harvesting mouse sciatic nerves of a maximum length that is sufficient for different analyses will be highly valuable. Here we describe a simple step-by-step guide for harvesting the maximum length of mouse sciatic nerve and compare the length of the harvested nerves gathered with the proposed method with nerves obtained using a conventional mid-thigh incision approach.
  7. Mansor NI, Ntimi CM, Abdul-Aziz NM, Ling KH, Adam A, Rosli R, et al.
    Bosn J Basic Med Sci, 2021 Feb 01;21(1):98-110.
    PMID: 32156249 DOI: 10.17305/bjbms.2020.4639
    One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.
  8. Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al.
    Cell Rep, 2019 01 29;26(5):1112-1127.e9.
    PMID: 30699343 DOI: 10.1016/j.celrep.2019.01.023
    The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.
  9. Wang M, Ling KH, Tan JJ, Lu CB
    Cells, 2020 06 18;9(6).
    PMID: 32570916 DOI: 10.3390/cells9061489
    Parkinson's Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.
  10. Mot YY, Moses EJ, Mohd Yusoff N, Ling KH, Yong YK, Tan JJ
    Cell Mol Neurobiol, 2023 Mar;43(2):469-489.
    PMID: 35103872 DOI: 10.1007/s10571-022-01201-y
    Traumatic brain injury (TBI) could result in life-long disabilities and death. Though the mechanical insult causes primary injury, the secondary injury due to dysregulated responses following neuronal apoptosis and inflammation is often the cause for more detrimental consequences. Mesenchymal stromal cell (MSC) has been extensively investigated as the emerging therapeutic for TBI, and the functional properties are chiefly attributed to their secretome, especially the exosomes. Delivering these nanosize exosomes have shown to ameliorate post-traumatic injury and restore brain functions. Recent technology advances also allow engineering MSC-derived exosomes to carry specific biomolecules of interest to augment their therapeutic outcome. In this review, we discuss the pathophysiology of TBI and summarize the recent progress in the applications of MSCs-derived exosomes, the roles and the signalling mechanisms underlying the protective effects in the treatment of the TBI.
  11. Lam XJ, Maniam S, Cheah PS, Ling KH
    Cell Mol Neurobiol, 2023 Oct;43(7):3417-3433.
    PMID: 37517069 DOI: 10.1007/s10571-023-01394-w
    Repressor element-1 silencing transcription factor (REST) or also known as neuron-restrictive silencing factor (NRSF), is the key initiator of epigenetic neuronal gene-expression modification. Identification of a massive number of REST-targeted genes in the brain signifies its broad involvement in maintaining the functionality of the nervous system. Additionally, REST plays a crucial role in conferring neuroprotection to the neurons against various stressors or insults during injuries. At the cellular level, nuclear localisation of REST is a key determinant for the functional transcriptional regulation of REST towards its target genes. Emerging studies reveal the implication of REST nuclear mislocalisation or dysregulation in several neurological diseases. The expression of REST varies depending on different types of neurological disorders, which has created challenges in the discovery of REST-targeted interventions. Hence, this review presents a comprehensive summary on the physiological roles of REST throughout brain development and its implications in neurodegenerative and neurodevelopmental disorders, brain tumours and cerebrovascular diseases. This review offers valuable insights to the development of potential therapeutic approaches targeting REST to improve pathologies in the brain. The important roles of REST as a key player in the nervous system development, and its implications in several neurological diseases.
  12. Mansor NI, Nordin N, Mohamed F, Ling KH, Rosli R, Hassan Z
    Curr Drug Deliv, 2019;16(8):698-711.
    PMID: 31456519 DOI: 10.2174/1567201816666190828153017
    Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.
  13. Ijabi R, Kaminsky ZA, Roozehdar P, Ijabi J, Moradi-Sardareh H, Ling KH, et al.
    Curr Med Chem, 2023 Sep 15.
    PMID: 37724672 DOI: 10.2174/0929867331666230915103147
    BACKGROUND: Epilepsy and intraventricular-cerebral hemorrhage is a common complication irreversible in preterm infants. Inflammation leads to an increase in intracellular calcium, acidosis, and oxygen usage, and finally, may damage brain cells. Increases in HIF-1a and HVCN1 can reduce the complications of oxygen consumption and acidosis in infants with intraventricular hemorrhage (IVH). On the other hand, decreases in S100B can shield nerve cells from apoptosis and epilepsy by reducing brain damage.

    OBJECTIVE: In this research, we investigated how miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 affect apoptosis in hypoxic mice.

    METHODS: On the first and third days after delivery, the YKL40, HIF-1a, HVCN1, and S100b genes were compared between two groups of preterm infants with and without maternal inflammation. Afterward, the miRNAs were transfected into cell lines to monitor variations in YKL40, HIF-1a, HVCN1, and S100b gene expression and nerve cell apoptosis. We changed the expression of S100b, HVCN1, and HIF-1a genes by using specific siRNAs injected into mice. Using real-time PCR, Western blotting, flow cytometry (FCM), and immunofluorescence, and changes in gene expression were evaluated (IHC).

    RESULTS: HVCN1 gene expression showed a strong negative correlation with epilepsy in both groups of infants (P<0.001). Significant correlations between epilepsy and the expression levels of the S100b, YKL40, and HIF-1a genes were found (P<0.001). According to FCM, after transfecting miRNA-431 and miRNA-34a into cell lines, the apoptosis index (A.I.) were 41.6 3.3 and 34.5 5.2%, respectively, while the A.I. were 9.6 2.7 and 7.1 4.2% after transfecting miRNA-21 and miRNA-138. MiR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 were simultaneously injected into hypoxic mice, and IHC double-labeling revealed that this reduced apoptosis and seizures compared to the hypoxic group.

    CONCLUSION: Our findings demonstrate that miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 injections prevent cerebral ischemia-induced brain damage in hypoxia mice by increasing HVCN1 and HIF-1a and decreasing S100b, which in turn lessens apoptosis and epilepsy in hypoxic mice.

  14. Ling KH, Brautigan PJ, Moore S, Fraser R, Leong MP, Leong JW, et al.
    Data Brief, 2016 Jun;7:282-90.
    PMID: 26958646 DOI: 10.1016/j.dib.2016.01.045
    SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.
  15. Jabbarzadeh Kaboli P, Rahmat A, Ismail P, Ling KH
    Eur J Pharmacol, 2014 Oct 5;740:584-95.
    PMID: 24973693 DOI: 10.1016/j.ejphar.2014.06.025
    Breast cancer is the most common cancer among women worldwide and novel therapeutic agents are needed to treat this disease. The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors. This review will discuss recent studies and consider the application of new prospective approaches based on microRNAs and other crucial regulators for use in future studies to define the action of berberine in cancer. The effects of berberine on cancer cell survival and proliferation are also outlined.
  16. Siew WH, Tan KL, Babaei MA, Cheah PS, Ling KH
    PMID: 23596395 DOI: 10.3389/fncel.2013.00041
    Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)].
  17. Atshan SS, Shamsudin MN, Lung LT, Ling KH, Sekawi Z, Pei CP, et al.
    Gene, 2012 Feb 25;494(2):219-24.
    PMID: 22222139 DOI: 10.1016/j.gene.2011.12.010
    The development of fast, reliable and inexpensive phenol protocol is described for the isolation of RNA from bacterial biofilm producers. The method was tested on Staphylococcus aureus (S. aureus) and other biofilm-producing gram-negative microorganisms and provided the highest integrity of RNA recovery in comparison to other methods reported here. In parallel experiments, bacterial lysis with Qiagen, NucleoSpin RNAII, InnuREP RNA Mini, Trizol and MasterPure RNA extraction Kits using standard protocols consistently gave low RNA yields with an absence of integrity. The boiling method presented here yielded high concentration of RNA that was free from 16S and 23S rRNA, contained 5S RNA. Higher yields due to improved biofilm bacterial cell lysis were achieved with an added hot phenol incubation step without the need for a bead mill or the enzyme. This method when used in conjunction with the Qiagen RNeasy Mini kit, RNA isolation was a success with greater integrity and contained undegraded 16S and 23S rRNA and did not require further purification. Contaminating DNA was a problem with the RNA processing samples; we used quantitative real-time PCR (RT-qPCR) to measure the recovery of RNA from bacterial biofilm cells using the method described here.
  18. Zainal Abidin S, Fam SZ, Chong CE, Abdullah S, Cheah PS, Nordin N, et al.
    Gene, 2019 May 20;697:201-212.
    PMID: 30769142 DOI: 10.1016/j.gene.2019.02.014
    MicroRNA-3099 is highly expressed during neuronal differentiation and development of the central nervous system. Here we characterised the role of miR-3099 during neural differentiation and embryonic brain development using a stable and regulatable mouse embryonic stem cell culture system for miR-3099 expression and in utero electroporation of miR-3099 expression construct into E15.5 embryonic mouse brains. In the in vitro system, miR-3099 overexpression upregulated gene related to neuronal markers such as Tuj1, NeuN, Gat1, vGluT1 and vGluT2. In contrast, gene related to astrocyte markers (Gfap, S100β and Slc1a3) were suppressed upon overexpression of miR-3099. Furthermore, miR-3099 overexpression between E15.5 and E18.5 mouse embryonic brains led to disorganised neuronal migration potentially due to significantly decreased Gfap+ cells. Collectively, our results indicated that miR-3099 plays a role in modulating and regulating expression of key markers involved in neuronal differentiation. In silico analysis was also performed to identify miR-3099 homologues in the human genome, and candidates were validated by stem-loop RT-qPCR. Analysis of the miR-3099 seed sequence AGGCUA against human transcriptomes revealed that a potential miRNA, mds21 (Chr21:39186698-39186677) (GenBank accession ID: MK521584), was 100% identical to the miR-3099 seed sequence. Mds21 expression was observed and validated in various human cell lines (293FT, human Wharton's jelly and dental pulp mesenchymal stem cells, and MCF-7, MDA-MB-231, C-Sert, SW780, RT112, 5637, EJ28 and SH-SY5Y cells), with the highest levels detected in human mesenchymal stem cell lines. The analysis validated mds21 as a novel miRNA and a novel homologue of miR-3099 in the human genome.
  19. Hashem Boroojerdi M, Hosseinpour Sarmadi V, Maqbool M, Ling KH, Safarzadeh Kozani P, Safarzadeh Kozani P, et al.
    Gene, 2022 Feb 05;820:146218.
    PMID: 35134469 DOI: 10.1016/j.gene.2022.146218
    OBJECTIVES: Hematopoietic stem cells (HSCs) reside in a specialised microenvironment in the bone marrow, which is majorly composed of mesenchymal stem cells (MSCs) and its' derivatives. This study aimed to investigate the regulatory role of MSCs to decipher the cellular and humoral communications on HSCs' proliferation, self-renewal, and differentiation at the transcriptomic level.

    MATERIALS AND METHODS: Microarray assay was employed to analyse the gene expression profile of HSCs that imparted by MSCs during co-culture.

    RESULTS: The proliferation of human umbilical cord blood-derived HSCs (hUC-HSCs) markedly propagated when MSCs were used as the feeder layer, without disturbing the undifferentiated state of HSCs, and reduced the cell death of HSCs. Upon co-culture with MSCs, the global microarray analysis of HSCs disclosed 712 differentially expressed genes (DEGs) (561 up-regulated and 151 down-regulated). The dysregulations of various transcripts were enriched for cellular functions such as cell cycle (including CCND1), apoptosis (including TNF), and genes related to signalling pathways governing self-renewal, as well as WNT5A from the Wnt signalling pathway, MAPK, Hedgehog, FGF2 from FGF, Jak-STAT, and PITX2 from the TGF-β signalling pathway. To concur this, real-time quantitative PCR (RT-qPCR) was utilised for corroborating the microarray results from five of the most dysregulated genes.

    CONCLUSION: This study elucidates the underlying mechanisms of the mitogenic influences of MSCs on the propagation of HSCs. The exploitation of such mechanisms provides a potential means for achieving larger quantities of HSCs in vitro, thus obviating the need for manipulating their differentiation potential for clinical application.

  20. Mohd-Zin SW, Abdullah NL, Abdullah A, Greene ND, Cheah PS, Ling KH, et al.
    Genome, 2016 Jul;59(7):439-48.
    PMID: 27373307 DOI: 10.1139/gen-2015-0142
    The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4(rb-2J/rb-2J), is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or "hopping gait" phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4(rb-2J) corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4(rb-2J) allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein-protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype.
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