Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs

Credille, Kelly M.; Minor, J.S.; Barnhart, Kirstin; Lee, E.; Cox, Melissa L.; Tucker, Kayleen; Diegel, Kelly L.; Venta, Patrick J.; Hohl, Daniel; Huber, Marcel; Dunstan, Robert W.

doi:10.1111/j.1365-2133.2009.09161.x

Cited by 52 publications

(50 citation statements)

References 22 publications

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“…In dogs, this disorder has been well characterized only in the Norfolk terrier (keratin 10, KRT10 ) [12]. In addition to ABDs, nonepidermolytic ARCI occurs in the Jack Russell terrier due to a defective structural protein (transglutaminase 1, TGM1 ) [13] and in great Danes due to a defect in a fatty acid transporter protein ( FATP4 aka SLC27A4 ) [19, 20]. A relatively common form of ARCI affects golden retrievers and, similar to ABDs, it is associated with a gene involved in epidermal lipid metabolism (phospholipase gene, PNPLA1 ) [14].…”

Section: Discussionmentioning

confidence: 99%

A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs

et al. 2017

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Autosomal recessive congenital ichthyosis in the American bulldog is characterized by generalized scaling and erythema with adherent scale on the glabrous skin. We had previously linked this disorder to NIPAL4, which encodes the protein ichthyin. Sequencing of NIPAL4 revealed a homozygous single base deletion (CanFam3.1 canine reference genome sequence NC_06586.3 g.52737379del), the 157th base (cytosine) in exon 6 of NIPAL4 as the most likely causative variant in affected dogs. This frameshift deletion results in a premature stop codon producing a truncated and defective NIPAL4 (ichthyin) protein of 248 amino acids instead of the wild-type length of 404. Obligate carriers were confirmed to be heterozygous for this variant, and 150 clinically non-affected dogs of other breeds were homozygous for the wild-type gene. Among 800 American bulldogs tested, 34% of clinically healthy dogs were discovered to be heterozygous for the defective allele. More importantly, the development of this canine model of autosomal recessive congenital ichthyosis will provide insight into the development of new treatments across species.

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Section: Discussionmentioning

confidence: 99%

A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs

et al. 2017

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“…TGM1-deficient lamellar ichthyosis in Jack Russell Terriers is also characterized by Malassezia overgrowth. 5 Malassezia are commensal yeast in the skin of dogs, as well as many other species. In dogs, Malassezia become opportunistic pathogens in the presence of predisposing factors such as allergic skin disease.…”

Section: Discussionmentioning

confidence: 99%

“…To date, a novel LINE-1 insertion in TGM1 has been identified as a cause of LI in related Jack Russell Terriers. 5 Recently, ACRI in Golden Retrievers has been associated with PNPLA1 mutations. 15 …”

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confidence: 99%

Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency

et al. 2014

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A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICH-THYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5′ upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species.

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“…[8][9][10][11] The effect of these mutations on the skin barrier can be demonstrated by the following examples. A mutation in K10 in Norfolk terriers leads to altered release of lamellar bodies, decreased exocytosis and reduced amount of intercellular lipid deposits, which are subsequently associated with increased TEWL.…”

Section: Domenico Santoro Answered That Thismentioning

confidence: 99%

Epidermal Barrier Function

Nishifuji¹,

Bizikova²

2013

Advances in Veterinary Dermatology

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Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs

Abstract: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.

Cited by 52 publications

References 22 publications

A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs

A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs

Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency

Epidermal Barrier Function

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