An antisense oligonucleotide efficiently suppresses splicing of an alternative exon in vascular smooth muscle in vivo.

Targeting alternative exons for therapeutic gain has been achieved in a few instances and potentially could be applied more broadly. The myosin phosphatase (MP) enzyme is a critical hub upon which signals converge to regulate vessel tone. Alternative exon 24 of myosin phosphatase regulatory subunit (Mypt1 E24) is an ideal target as toggling between the two isoforms sets smooth muscle sensitivity to vasodilators such as nitric oxide (NO). This study aimed to develop a gene-based therapy to suppress splicing of Mypt1 E24 thereby switching MP enzyme to the NO-responsive isoform. CRISPR/Cas9 constructs were effective at editing of Mypt1 E24 in vitro; however, targeting of vascular smooth muscle in vivo with AAV9 was inefficient. In contrast, an octo-guanidine conjugated antisense oligonucleotide targeting the 5' splice site of Mypt1 E24 was highly efficient in vivo. It reduced the percent splicing inclusion of Mypt1 E24 from 80% to 10% in mesenteric arteries. The maximal and half-maximal effects occurred at 12.5 and 6.25 mg/kg, respectively. The effect persisted for at least 1 mo without toxicity. This highly effective splice-blocking antisense oligonucleotide could be developed as a novel therapy to reverse vascular dysfunction common to diseases such as hypertension and heart failure.NEW & NOTEWORTHY Alternative exon usage is a major driver of phenotypic diversity in all cell types including smooth muscle. However, the functional significance of most of the hundreds of thousands of alternative exons has not been defined, nor in most cases even tested. If their importance to vascular function were known these alternative exons could represent novel therapeutic targets. Here, we present injection of Vivo-morpholino splice-blocking antisense oligonucleotides as a simple, efficient, and cost-effective method for suppression of alternative exon usage in vascular smooth muscle in vivo.

Air or Ground Transport to the Critical Care Resuscitation Unit: Does It Really Matter?

OBJECTIVE: Critically ill patients requiring urgent interventions or subspecialty care often require transport over significant distances to tertiary care centers. The optimal method of transportation (air vs. ground) is unknown. We investigated whether air transport was associated with lower mortality for patients being transferred to a specialized critical care resuscitation unit (CCRU). METHODS: This was a retrospective study of all adult patients transferred to the CCRU at the University of Maryland Medical Center in 2018. Our primary outcome was hospital mortality. The secondary outcomes included the length of stay and the time to the operating room (OR) for patients undergoing urgent procedures. We performed optimal 1:2 propensity score matching for each patient's need for air transport. RESULTS: We matched 198 patients transported by air to 382 patients transported by ground. There was no significant difference between demographics, the initial Sequential Organ Failure Assessment score, or hospital outcomes between groups. One hundred sixty-four (83%) of the patients transported via air survived to hospital discharge compared with 307 (80%) of those transported by ground (P = .46). Patients transported via air arrived at the CCRU more quickly (127 [100-178] vs. 223 [144-332] minutes, P < .001) and were more likely (60 patients, 30%) to undergo urgent surgical operation within 12 hours of CCRU arrival (30% vs. 17%, P < .001). For patients taken to the OR within 12 hours of arriving at the CCRU, patients transported by air were more likely to go to the OR after 200 minutes since the transfer request (P = .001). CONCLUSION: The transportation mode used to facilitate interfacility transfer was not significantly associated with hospital mortality or the length of stay for critically ill patients.

Case report: novel PCDH15 variant causes usher syndrome type 1F with congenital hearing loss and syndromic retinitis pigmentosa.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene. CASE PRESENTATION: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F. CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.

Association between resuscitation in the critical care resuscitation unit and in-hospital mortality.

INTRODUCTION: Patients who present in shock have high expected mortality and early resuscitation is crucial to improve their outcomes. The Critical Care Resuscitation Unit (CCRU) is a specialized unit at the University of Maryland Medical Center (UMMC) that prioritizes early resuscitation of critically ill patients. We hypothesized that lactate clearance and reduction of Sequential Organ Failure Assessment (SOFA) score during CCRU stay would be associated with lower in-hospital mortality. METHODS: We performed a retrospective analysis of adult patients who were admitted to the CCRU between 01/01/2018-12/31/2018 and had a diagnosis of severe shock, determined by serum lactate ≥4 mmol/L. We excluded patients who died during CCRU stay. We used multivariable logistic regression to evaluate the association between lactate clearance and reduction in SOFA scores during CCRU stay and in-hospital mortality. RESULTS: Out of 1740 patients admitted to the CCRU in 2018, 172 (10%) had serum lactate ≥4 mmol/L. Twenty-two (13%) patients died during their CCRU stay. Our primary analysis included 129 patients with lactate clearance data and 136 patients with SOFA data. Average patients' age was 54 years, and median length of stay in the CCRU was 6 h 55 min. The average lactate and SOFA score on admission were 7.4 (3.8) mmol/L and 8.3 (4.7), respectively. Average lactate clearance was 1.9 (3.1) and average SOFA score reduction was 0.2 (2.9). In multivariable logistic regressions evaluating SOFA score and lactate separately, SOFA score reduction during CCRU stay was associated with lower in-hospital mortality (OR 0.83, 95% CI: 0.70-0.97) but lactate clearance was not (OR 0.90, 95% CI 0.78-1.03). In forward stepwise multivariable analysis containing both SOFA score and lactate values, SOFA score clearance during CCRU stay was still associated with decreased in-hospital mortality (OR 0.84, 95% CI 0.72-0.98). CONCLUSIONS: Care in the CCRU is more effective at reducing lactate than SOFA scores in patients with severe shock. However, SOFA score reduction in the resuscitation phase during the CCRU stay was associated with decreased odds of in-hospital mortality in this group of patients. Further studies are necessary to confirm our observations.

Congenital Stationary Night Blindness: Clinical and Genetic Features.

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

Mouse Models of Achromatopsia in Addressing Temporal "Point of No Return" in Gene-Therapy.

Achromatopsia is characterized by amblyopia, photophobia, nystagmus, and color blindness. Previous animal models of achromatopsia have shown promising results using gene augmentation to restore cone function. However, the optimal therapeutic window to elicit recovery remains unknown. Here, we attempted two rounds of gene augmentation to generate recoverable mouse models of achromatopsia including a Cnga3 model with a knock-in stop cassette in intron 5 using Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR) and targeted embryonic stem (ES) cells. This model demonstrated that only 20% of CNGA3 levels in homozygotes derived from target ES cells remained, as compared to normal CNGA3 levels. Despite the low percentage of remaining protein, the knock-in mouse model continued to generate normal cone phototransduction. Our results showed that a small amount of normal CNGA3 protein is sufficient to form "functional" CNG channels and achieve physiological demand for proper cone phototransduction. Thus, it can be concluded that mutating the Cnga3 locus to disrupt the functional tetrameric CNG channels may ultimately require more potent STOP cassettes to generate a reversible achromatopsia mouse model. Our data also possess implications for future CNGA3-associated achromatopsia clinical trials, whereby restoration of only 20% functional CNGA3 protein may be sufficient to form functional CNG channels and thus rescue cone response.

Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins.

Tannins, polyphenols in medicinal plants, have been divided into two groups of hydrolysable and condensed tannins, including gallotannins, ellagitannins, and (-)-epigallocatechin-3-gallate (EGCG). Potent anticancer activities have been observed in tannins (especially EGCG) with multiple mechanisms, such as apoptosis, cell cycle arrest, and inhibition of invasion and metastases. Furthermore, the combinational effects of tannins and anticancer drugs have been demonstrated in this review, including chemoprotective, chemosensitive, and antagonizing effects accompanying with anticancer effect. However, the applications of tannins have been hindered due to their poor liposolubility, low bioavailability, off-taste, and shorter half-life time in human body, such as EGCG, gallic acid, and ellagic acid. To tackle these obstacles, novel drug delivery systems have been employed to deliver tannins with the aim of improving their applications, such as gelatin nanoparticles, micelles, nanogold, liposomes, and so on. In this review, the chemical characteristics, anticancer properties, and drug delivery systems of tannins were discussed with an attempt to provide a systemic reference to promote the development of tannins as anticancer agents.

ESI MS for Microsized Bioparticles.

An ESI ion trap mass spectrometer was designed for high-throughput and rapid mass analysis of large bioparticles. Mass calibration of the instrument was performed using commercially available polystyrene (PS) microparticles with a size comparable to cancer cells. Different sizes of MCF-7 breast cancer cells (8 to 15 µm) were used in this study. The masses of different cancer cells were measured. This system allows for the analysis of all types of particles.

Technical Failure of MR Elastography Examinations of the Liver: Experience from a Large Single-Center Study.

Purpose To assess the determinants of technical failure of magnetic resonance (MR) elastography of the liver in a large single-center study. Materials and Methods This retrospective study was approved by the institutional review board. Seven hundred eighty-one MR elastography examinations performed in 691 consecutive patients (mean age, 58 years; male patients, 434 [62.8%]) in a single center between June 2013 and August 2014 were retrospectively evaluated. MR elastography was performed at 3.0 T (n = 443) or 1.5 T (n = 338) by using a gradient-recalled-echo pulse sequence. MR elastography and anatomic image analysis were performed by two observers. Additional observers measured liver T2* and fat fraction. Technical failure was defined as no pixel value with a confidence index higher than 95% and/or no apparent shear waves imaged. Logistic regression analysis was performed to assess potential predictive factors of technical failure of MR elastography. Results The technical failure rate of MR elastography at 1.5 T was 3.5% (12 of 338), while it was higher, 15.3% (68 of 443), at 3.0 T. On the basis of univariate analysis, body mass index, liver iron deposition, massive ascites, use of 3.0 T, presence of cirrhosis, and alcoholic liver disease were all significantly associated with failure of MR elastography (P < .004); but on the basis of multivariable analysis, only body mass index, liver iron deposition, massive ascites, and use of 3.0 T were significantly associated with failure of MR elastography (P < .004). Conclusion The technical failure rate of MR elastography with a gradient-recalled-echo pulse sequence was low at 1.5 T but substantially higher at 3.0 T. Massive ascites, iron deposition, and high body mass index were additional independent factors associated with failure of MR elastography of the liver with a two-dimensional gradient-recalled-echo pulse sequence. © RSNA, 2017.

Solitary fibrous tumour of the liver-report on metastasis and local recurrence of a malignant case and review of literature.

BACKGROUND: Solitary fibrous tumours (SFT) are neoplasms of mesenchymal origin that predominantly arise from the pleura. SFT of the liver (SFTL) are a rare occurrence with little number of cases reported in English literature. Malignant cases of hepatic SFT are an even rarer occurrence. For this reason, the prognostic evaluation of SFTLs is unknown and difficult to measure. METHODS: A search on English literature on "Solitary Fibrous Tumour of the Liver" was conducted on common search engines (PubMed, Google). All published articles, case reports and literature reviews and their reference lists were reviewed. CASE REPORT: This paper presents a 61-year-old male who was referred to a tertiary hospital in April 2010 with marked hepatomegaly. USS, CT and MRI scans were suggestive of a neoplasm, and the patient underwent a subsegmental IVb resection in June 2010. The specimen demonstrated histological and immunohistochemical features of malignant SFTL with clear resection margins. The patient was followed up regularly for 3 years with imaging and no suggestion of recurrence. Six years after the initial surgery, the patient represented with worsening right upper quadrant pain and dyspnoea secondary to extensive tumour recurrence adjacent to the resection site and metastatic deposits in the pleura. The patient was managed symptomatically and discharged for community follow-up after palliative involvement. CONCLUSIONS: SFTL are rare with only 84 cases reported in the English Literature including the present case. The average age of patients is 57.1 and occurs in females more than males (1.4:1). Most SFTLs follow a benign course, however, 17.9% of cases displayed malignant histological features. Only three cases including the current case are reported to have both local recurrence and metastasis. Surgical resection remains the mainstay of treatment and appears to be curative of most cases. The rarity of this tumour makes it difficult to evaluate its prognosis and natural course.

Uniqueness: skews bit occurrence frequencies in randomly generated fingerprint libraries.

Requiring that randomly generated chemical fingerprint libraries have unique fingerprints such that no two fingerprints are identical causes a systematic skew in bit occurrence frequencies, the proportion at which specified bits are set. Observed frequencies (O) at which each bit is set within the resulting libraries systematically differ from frequencies at which bits are set at fingerprint generation (E). Observed frequencies systematically skew toward 0.5, with the effect being more pronounced as library size approaches the compound space, which is the total number of unique possible fingerprints given the number of bit positions each fingerprint contains. The effect is quantified for varying library sizes as a fraction of the overall compound space, and for changes in the specified frequency E. The cause and implications for this systematic skew are subsequently discussed. When generating random libraries of chemical fingerprints, the imposition of a uniqueness requirement should either be avoided or taken into account.

Selective killing of cancer cells by nanoparticle-assisted ultrasound.

BACKGROUND: Intense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells. RESULTS: Co-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, respectively, were treated with focused ultrasound beams with the addition of gold and magnetic nanoparticles. There were significantly more necrotic A549 cells than BEAS-2 cells when gold nanoparticles were added to the culture medium [(50.6 ± 15.1) vs. (7.4 ± 2.9) %, respectively, P < 0.01]. This selective damage to cancer cells was also observed for MDA-MB231 breast cancer cells relative to MCF-10A normal breast cells after treatment with magnetic nanoparticles. CONCLUSIONS: The data obtained for different cell lines indicate that nanoparticle-assisted ultrasound therapy (NAUT) could be an effective new tool for cancer-specific treatment and could potentially be combined with conventional methods of cancer diagnosis and therapy to further increase the overall cancer cure rate.

Elastin degradation by cathepsin V requires two exosites.

Cathepsin V is a highly effective elastase and has been implicated in physiological and pathological extracellular matrix degradation. However, its mechanism of action remains elusive. Whereas human cathepsin V exhibits a potent elastolytic activity, the structurally homologous cathepsin L, which shares a 78% amino acid sequence, has only a minimal proteolytic activity toward insoluble elastin. This suggests that there are distinct structural domains that play an important role in elastinolysis. In this study, a total of 11 chimeras of cathepsins V and L were generated to identify elastin-binding domains in cathepsin V. Evaluation of these chimeras revealed two exosites contributing to the elastolytic activity of cathepsin V that are distant from the active cleft of the protease and are located in surface loop regions. Replacement of exosite 1 or 2 with analogous residues from cathepsin L led to a 75 and 43% loss in the elastolytic activity, respectively. Replacement of both exosites yielded a non-elastase variant similar to that of cathepsin L. Identification of these exosites may contribute to the design of inhibitors that will only affect the elastolytic activity of cysteine cathepsins without interfering with other physiological protease functions.

Panniculectomy for a Rare End-Stage Complication of Severe Obesity and Increasing Surgical Phenomenon.

Panniculus morbidus (PM) is a presentation of severe chronic abdominal lymphoedema associated with obesity resulting in oedema and chronic fibrosis. It is a multifaceted condition with significant clinical and psychosocial implications. A 29-year-old female weighing 260 kg with a body mass index of 95 kg/m2 had recurrent infections and sepsis associated with an abdominal pannus extending to her knees and an area of ulceration. The pannus was indurated with extensive fibrosis that significantly affected her quality of life (QOL) requiring assistance for all activities of daily living (ADLs). A panniculectomy was performed with a negative pressure skin dressing over the skin wound. She was discharged after two days. Two months postoperatively, she reported significant improvement in QOL and can now mobilise and perform ADLs independently with no recurrent admissions. The global prevalence of obesity is reaching pandemic proportions and so will its complications. It can be functionally debilitating and worsen obesity. Surgical resection is indicated to restore mobility and function, prevent recurrent infections, improve QOL, and reduce economic burden. Patients report high satisfaction rates following surgery. Panniculectomy is an effective treatment to alleviate morbidity in severe obesity and should be considered in patients with recurrent infections and a significant impact on QOL.

Introduction and Discovery of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy. There are three main characteristics of RP: night blindness, retinal pigmentation, and visual field constriction. Among these three features, night blindness was the first to be discovered, which could be dated back to the ancient Egyptians at around 1500 BC. However, the night blindness described at that time was most likely associated with vitamin A deficiency rather than RP. Retinitis pigmentosa was first described in cadaver anatomic dissection before the invention of the ophthalmoscope. However, it was not linked to RP or night blindness. It was not until the invention of the ophthalmoscope that ophthalmologists could truly look into the eye and correlate the retinal pigmentation with clinical symptoms, such as night blindness and visual field constriction. In 1983, at a RP workshop that gathered together many experts, a consensus was reached regarding the terminology and guidelines for the diagnosis of RP. In this chapter, we will introduce the history and discovery of RP along with its characteristics.

Pneumomediastinum and Pericardium During Labour: A Report on a Rare Postpartum Phenomenon.

Hamman's syndrome (HS) is characterised by spontaneous pneumomediastinum and subcutaneous emphysema. It is a rare phenomenon that can occur during labour. Its incidence is 1 in 100,000 births and predominantly affects young primiparous women with prolonged labour. Patients commonly present with subcutaneous emphysema, chest pain, and dyspnoea. We present the case of a 20-year-old primigravida female with no other medical history who had prolonged labour at 43 weeks gestation. Sudden-onset, right-sided cheek pain and swelling was noted immediately after delivery accompanied by pleuritic chest pain. Chest X-ray (CXR) and computed tomography (CT) demonstrated significant pneumomediastinum and pneumopericardium with subcutaneous emphysema extending to the neck. She was managed symptomatically in addition to antibiotics and discharged after three days with complete resolution of symptoms. No concerns were raised during the follow-up. HS is a rare phenomenon that can occur during labour, particularly in young primiparous females with a prolonged second stage. Radiological investigations in the form of CXR and CT are recommended to rule out life-threatening complications and other conditions that may require immediate management. HS occurs due to rupture of peripheral alveoli secondary to increased intrathoracic pressures from excessive Valsalva manoeuvre allowing air to dissect and enter into the mediastinum. Pneumopericardium in association with HS is extremely rare. It is particularly clinically important because it can cause cardiac tamponade requiring immediate surgical management. HS is otherwise a self-limiting condition and management is symptomatic only. Our case is unique due to the presence of pneumopericardium in association with HS, the fourth ever reported in the literature. Due to its rarity, the incidence of tamponade in this cohort of patients is yet to be delineated.

Appendiceal diverticulitis and inflammatory bowel disease.

Appendiceal diverticulitis is known as a rare pathology and its etiology remains largely unknown. We describe a case of a 41-year-old woman with a past history of inflammatory bowel disease (IBD) who was admitted to the Emergency Department at a rural hospital in Australia with right iliac fossa pain (RIF) and later was found to have acute appendiceal diverticulitis on histopathologic studies. Thus far, no literature has described IBD as one of the possible contributing factors of appendiceal diverticulitis. This paper aims to shed light on the possible causative relation between appendiceal diverticulitis and IBD.

Examining Predictors of Early Admission and Transfer to the Critical Care Resuscitation Unit.

INTRODUCTION: Previous studies have demonstrated that rapid transfer to definitive care improves the outcomes for many time-sensitive conditions. The critical care resuscitation unit (CCRU) improves the operations of the University of Maryland Medical Center (UMMC) by expediting the transfers and resuscitations for critically ill patients who exceed the resources at other facilities. In this study we investigated CCRU transfer patterns to determine patient characteristics and logistical factors that influence bed assignments and transfer to the CCRU. We hypothesized that CCRU physicians prioritize transfer for critically ill patients. Therefore, those patients would be transferred faster. METHODS: We performed a retrospective review of all non-traumatic adult patients transferred to the CCRU from other hospitals between January 1-December 31, 2018. The primary outcome was the interval from transfer request to CCRU bed assignment. The secondary outcome was the interval from transfer request to CCRU arrival. We used multivariate logistic regressions to determine associations with the outcomes of interest. RESULTS: A total of 1,741 patients were admitted to the CCRU during the 2018 calendar year. Of those patients, 1,422 were transferred from other facilities and were included in the final analysis. Patients' mean age was 57 ± 17 years with a median Sequential Organ Failure Assessment (SOFA) score of 3 [interquartile range 1-6]. Median time from transfer request to CCRU bed assignment was 8 (0-70) minutes. A total of 776 (55%) patients underwent surgical intervention after arrival. Using the median transfer request to bed assignment time, we found that patients requiring stroke neurology (odds ratio [OR] 5.49, 95% confidence interval [CI] 2.85-10.86), having higher SOFA score (OR 1.04, 95% CI 1.001-1.07), and needing an immediate operation (OR 2.85, 95% CI 1.98-4.13) were associated with immediate bed assignment time (≤8 minutes). Patients who were operated on (OR 0.74, 95% CI 0.55-0.99) were significantly less likely to have an immediate bed assignment time. CONCLUSION: The CCRU expedited the transfer of critically ill patients who needed urgent interventions from outside facilities. Higher SOFA scores and the need for urgent neurological or surgical intervention were associated with near-immediate CCRU bed assignment. Other institutions with similar models to the CCRU should perform studies to confirm our observations.

Spatiotemporal control of genome engineering in cone photoreceptors.

BACKGROUND: Cones are essential for color recognition, high resolution, and central vision; therefore cone death causes blindness. Understanding the pathophysiology of each cell type in the retina is key to developing therapies for retinal diseases. However, studying the biology of cone cells in the rod-dominant mammalian retina is particularly challenging. In this study, we used a bacterial artificial chromosome (BAC) recombineering method to knock in the "CreERT2" sequence into the Gnat2 and Arr3 genes, respectively and generated three novel inducible CreERT2 mice with different cone cell specificities. RESULTS: These models (Gnat2CreERT2, Arr3T2ACreERT2, and Arr3P2ACreERT2) express temporally controllable Cre recombinase that achieves conditional alleles in cone photoreceptors. Cre-LoxP recombination can be induced as early as postnatal day (PD) two upon tamoxifen injection at varying efficiencies, ranging from 10 to 15% in Gnat2CreERT2, 40% in Arr3T2ACreERT2, and 100% in Arr3P2ACreERT2. Notably, knocking in the P2A-CreERT2 cassette does not affect cone cell morphology and functionality. Most cone-phototransduction enzymes, including Opsins, CNGA3, etc. are not altered except for a reduction in the Arr3 transcript. CONCLUSIONS: The Arr3P2ACreERT2 mouse, an inducible cone-specific Cre driver, is a valuable line in studying cone cell biology, function, as well as its relationship with rod and other retinal cells. Moreover, the Cre activity can be induced by delivering tamoxifen intragastrically as early as PD2, which will be useful for studying retinal development or in rapid degenerative mouse models.