Abstract:
:Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Barraza-Flores P,Fontelonga TM,Wuebbles RD,Hermann HJ,Nunes AM,Kornegay JN,Burkin DJdoi
10.1093/hmg/ddz086subject
Has Abstractpub_date
2019-08-15 00:00:00pages
2686-2695issue
16eissn
0964-6906issn
1460-2083pii
5479258journal_volume
28pub_type
杂志文章abstract::Pathological modifications in the microtubule-associated protein Tau is a common characteristic observed in different neurological diseases, suggesting that analogous metabolic pathways might be similarly affected during neurodegeneration. To identify these molecules and mechanisms, we utilized Drosophila models of hu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu393
更新日期:2014-12-20 00:00:00
abstract::Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. We report here on consortin, a novel integral membrane protein that is predicted to be i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp490
更新日期:2010-01-15 00:00:00
abstract::Uniparental disomy (UPD) is defined as the inheritance of both homologs of a given genomic region from only one parent. The majority of UPD includes an entire chromosome. However, the extent of UPD is sometimes limited to a subchromosomal region (segmental UPD). Mosaic paternal UPD (pUPD) of chromosome 11 is found in ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw023
更新日期:2016-04-01 00:00:00
abstract::Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindn...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh198
更新日期:2004-09-01 00:00:00
abstract::Even though heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors, previous studies have not explained a large part of the genetics behind these diseases. In this genome-wide association study, we include 346 545 Caucasians from the UK Biobank to identify novel ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz175
更新日期:2019-12-01 00:00:00
abstract::LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.25.2869
更新日期:2001-12-01 00:00:00
abstract::Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes. Understanding the normal function of this essential protein is vital to u...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl467
更新日期:2007-02-15 00:00:00
abstract::The role of renin binding protein (RnBP) in human (patho)physiology, despite its biochemical characterization, is as yet unclear. RnBP has been shown to bind and inactivate renin, a key player of the blood pressure regulating renin-angiotensin system. This renders the RnBP gene a promising candidate gene in human hype...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1527
更新日期:1997-09-01 00:00:00
abstract::There are two known mRNA degradation pathways, 3' to 5' and 5' to 3'. We identified likely pathogenic variants in two genes involved in these two pathways in individuals with intellectual disability. In a large family with multiple branches, we identified biallelic variants in DCPS in three affected individuals; a spl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv069
更新日期:2015-06-01 00:00:00
abstract::By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.9.1445
更新日期:1997-09-01 00:00:00
abstract::Polyglutamine expansions in the huntingtin gene cause Huntington's disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterations also in peripheral organs. Variations in the length of the polyglutamine tract explain up to 70% of the age-at-onset variance, with the rest of the variance attribu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy077
更新日期:2018-05-15 00:00:00
abstract::Functional and genomic approaches can be integrated to screen efficiently for pathogenic alleles in founder populations. We applied such approaches to analysis of the cancer-associated cell cycle regulator CHEK2 in the Ashkenazi Jewish population. We first identified two extended haplotypes at CHEK2 that co-segregated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi052
更新日期:2005-02-15 00:00:00
abstract::The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw383
更新日期:2017-01-15 00:00:00
abstract::Complement receptor 1 (CR1) is an Alzheimer's disease (AD) susceptibility locus that also influences AD-related traits such as episodic memory decline and neuritic amyloid plaque deposition. We implemented a functional fine-mapping approach, leveraging intermediate phenotypes to identify functional variant(s) within t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds054
更新日期:2012-05-15 00:00:00
abstract::NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr214
更新日期:2011-08-15 00:00:00
abstract::Multiple research groups have observed neuropathological phenotypes and molecular symptoms in vitro using induced pluripotent stem cell (iPSC)-derived neural cell cultures (i.e. patient-specific neurons and glia). However, the global differences/similarities that may exist between in vitro neural cells and their tissu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt208
更新日期:2013-09-01 00:00:00
abstract::The high affinity receptor for IgE (Fc epsilon RI) has a central role in mast cell degranulation and IgE mediated allergy. A systematic search through the coding regions of the beta subunit of Fc epsilon RI (Fc epsilon RI-beta) has identified a novel coding polymorphism in exon seven. An adenine to guanine substitutio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.7.959
更新日期:1996-07-01 00:00:00
abstract::Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx178
更新日期:2017-08-15 00:00:00
abstract::Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double-stranded breaks and response to oxidative stress. We show that CRISPR/Cas9-assisted gene correction combined with piggyBac (PB) transposon-mediated excision of the selection cassette enables seamle...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa023
更新日期:2020-04-15 00:00:00
abstract::Elucidating the molecular changes that arise during neural differentiation and fate specification is crucial for building accurate in vitro models of neurodegenerative diseases using human embryonic stem cells (hESCs). Here we review the importance of hESCs and derived progenitors in treating and modeling neurological...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddn065
更新日期:2008-04-15 00:00:00
abstract::Recombination was measured across nine intervals in the human beta-globin gene cluster by single-sperm analysis. A recombination fraction of approximately 0.9% was calculated across an approximately 11 kb region using a new method to estimate recombination fractions from single-sperm typing data. No recombination was ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.3.207
更新日期:2002-02-01 00:00:00
abstract::Cytosolic accumulation of TAR DNA binding protein 43 (TDP-43) is a major neuropathological feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the mechanisms involved in TDP-43 accumulation remain largely unknown. Previously, we reported that inhibitors of cyclin-depen...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu578
更新日期:2015-03-15 00:00:00
abstract::Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent finding in hairy cell leukemia (HCL). We have previously identified a number of candidate genes localized in close proximity to a constitutional inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta-hexosaminodase HEXB, f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh315
更新日期:2004-12-01 00:00:00
abstract::Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connec...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx110
更新日期:2017-06-15 00:00:00
abstract::Mutations in the MYOC gene may lead to juvenile open-angle glaucoma with high intraocular pressure, and are detected in about 4% of people with adult onset glaucoma. Most of these mutations are found in the third exon of the gene encoding the olfactomedin-like domain located at the C terminus of the protein. Another o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.11.1291
更新日期:2002-05-15 00:00:00
abstract::Genetic variants in one-carbon folate metabolism have been identified as risk factors for disease because they may impair the production or use of one-carbon folates required for nucleotide synthesis and methylation. p.R653Q (1958G>A) is a single-nucleotide polymorphism (SNP) in the 10-formyltetrahydrofolate (formylTH...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt223
更新日期:2013-09-15 00:00:00
abstract::Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE le...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.1.27
更新日期:1998-01-01 00:00:00
abstract::DNA methylation (DNAm) has been linked to changes in chromatin structure, gene expression and disease. The DNAm level can be affected by genetic variation; although, how this differs by CpG dinucleotide density and genic location of the DNAm site is not well understood. Moreover, the effect of disease causing variants...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw072
更新日期:2016-06-15 00:00:00
abstract::Lysosomal storage diseases are due to inherited deficiencies in various enzymes involved in basic metabolic processes. As with other genetic diseases, accurate structure data for these enzymatic proteins should help in better understanding the molecular effects of mutations identified in patients with the correspondin...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.6.967
更新日期:2000-04-12 00:00:00
abstract::Sonic Hedgehog (SHH) is one of the most intensively studied genes in developmental biology. It is a highly conserved gene, found in species as diverse as arthropods and mammals. The mammalian SHH encodes a signaling molecule that plays a central role in developmental patterning, especially of the nervous system and th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl123
更新日期:2006-07-01 00:00:00