The short mRNA isoform of the immunoglobulin superfamily, member 1 gene encodes an intracellular glycoprotein

Wang, Ying; Brûlé, Emilie; Silander, Tanya L; Bąk, Beata; Joustra, Sjoerd D; Bernard, Daniel J.

doi:10.1371/journal.pone.0180731

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…It is evident that medium and small sized dogs are more HAC affected, which could be explained by data from a study that compared gene expression among dog sizes, identifying variants regarding a lower expression of IRS-4, IGSF-1 and ACSL-4 in small and medium sized dogs (Plassais et al 2017). Such substrates are important in pituitary development (Wang et al 2017) and in steroidogenesis (Midzak & Papadopoulos 2016), which may explain the correlation between the occurrence of HAC and size. However, the breeds most reported in our study are also popular in our region, and the fact that they were overrepresented in this population does not absolutely means that they are more prone to HAC.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014)

et al. 2019

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Diseases’ clinical-epidemiological characterization assists in directing the diagnosis. The objective of this study was to describe epidemiological, clinical and laboratorial aspects of a case series of canine hyperadrenocorticism (HAC). One-hundred fifteen records of dogs diagnosed by the low dose dexamethasone suppression test and/or ACTH stimulation test were evaluated. Of the cases, 81.3% were HAC ACTH-dependent and 18.7% HAC ACTH-independent. Females were more affected, representing 69.3% of the cases. The mean age was 10.3±2.5 years and 64.9% were gonadectomized. Most of the patients were small size dogs, weighting less than 10kg (73.9%). The most frequent breeds were: Poodle (27%), Dachshund (17.4%), and Yorkshire Terrier (10.4%). The most frequent clinical manifestations were polyphagia (86%), polydipsia (82.6%), polyuria (80%), abdominal enlargement (82.6%), thin skin (79.1%), muscular weakness (78.3%) and panting (74.8%). However, eventually unusual HAC-associated signs would be present in some dogs in a more important way compared with the classic disease´s clinical signs. The CBC showed neutrophilia (66%), eosinopenia (58.3%) and lymphopenia (42.6%) as main hematological abnormalities. The most common findings in serum biochemistry were increased alkaline phosphatase activity (81.74%), increased ALT activity (62.6%), hypercholesterolemia (66%) and hypertriglyceridemia (54.7%). Urinalysis revealed hyposthenuria in 14.9% and isostenuria in 13.5%; besides proteinuria in 50% of the cases. Abdominal ultrasound showed bilateral adrenal hyperplasia (92.2%) with adrenal asymmetry in 20.8% of the cases, in addition to hepatomegaly (80.9%), biliary sludge (67.8%) and hepatic hyperechogenicity (47.8%). It was concluded that small size gonadectomized female dogs, mainly Poodles and Dachshunds, presented higher frequency in the population studied, and that the main changes observed in clinical and complementary tests were polyphagia, polyuria, polydipsia, abdominal enlargement, adrenal hyperplasia, increased phosphatase alkaline and hyperlipidemia. These results corroborated to a better disease characterization at Brazil. This work concluded that the population studied resembles the profile describe in European and North American epidemiologic studies, and that the HAC dog´s clinical picture looks similar worldwide.

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Section: Discussionmentioning

confidence: 99%

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014)

et al. 2019

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“…This transcript was predicted to encode a secreted protein containing the first two Ig loops of full-length IGSF1. Recent data, however, indicate that this isoform, which is also expressed in human pituitary, is retained in the ER, like the IGSF1-NTD (described above) [ 43 ]. Regardless, removal of the noncoding exon 1 eliminated detectable expression of both the full-length and truncated mRNA isoforms from pituitaries of Igsf1 Δex1 mice [ 14 ].…”

Section: Igsf1 Regulates Pituitary Responsiveness To Trhmentioning

confidence: 99%

From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function

Bernard

Brûlé

Smith

et al. 2018

Journal of the Endocrine Society

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Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo, failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1’s function in endocrine tissues, including the pituitary and testes.

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“…Multiple IGSF1/Igsf1 mRNA isoforms have been characterized in human and rodent pituitary glands [ 22 , 28 , 29 ]. The murine Igsf1 isoform 1 (IGSF1-1) transcript encodes the full-length IGSF1 protein, including both the NTD and CTD.…”

Section: Resultsmentioning

confidence: 99%

The extant immunoglobulin superfamily, member 1 gene results from an ancestral gene duplication in eutherian mammals

2022

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Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein with high expression in the mammalian pituitary gland. Mutations in the IGSF1 gene cause congenital central hypothyroidism in humans. The IGSF1 protein is co-translationally cleaved into N- and C-terminal domains (NTD and CTD), the latter of which is trafficked to the plasma membrane and appears to be the functional portion of the molecule. Though the IGSF1-NTD is retained in the endoplasmic reticulum and has no apparent function, it has a high degree of sequence identity with the IGSF1-CTD and is conserved across mammalian species. Based upon phylogenetic analyses, we propose that the ancestral IGSF1 gene encoded the IGSF1-CTD, which was duplicated and integrated immediately upstream of itself, yielding a larger protein encompassing the IGSF1-NTD and IGSF1-CTD. The selective pressures favoring the initial gene duplication and subsequent retention of a conserved IGSF1-NTD are unresolved.

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The short mRNA isoform of the immunoglobulin superfamily, member 1 gene encodes an intracellular glycoprotein

Cited by 4 publications

References 24 publications

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014)

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014)

From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function

The extant immunoglobulin superfamily, member 1 gene results from an ancestral gene duplication in eutherian mammals

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