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PubMed1985

Concentration of bronchoalveolar lavage fluid by ultrafiltration: evidence of differential protein loss and functional inactivation of proteinase inhibitors.

Bronchoalveolar lavage samples were concentrated using positive-pressure ultrafiltration. The starting material, concentrates, and eluates were assayed for immunoglobulin A (IgA), albumin (Alb), alpha 1-proteinase inhibitor (alpha 1-PI), antileukoprotease (ALP), and total leukocyte elastase inhibitory capacity (LEIC). No enzyme inhibitory capacity or protein was detected in membrane eluates, confirming the selectivity of the membrane used (Mr cutoff 2000 or 500). However, the concentrated lavages showed a generated loss of protein. The proportion of each protein recovered using the 500 Mr cutoff membrane was: IgA, 50.6% (+/- 15%); albumin, 43% (+/- 8.4); alpha 1-PI, 53.6 (+/- 17.3); ALP, 43% (+/- 2.1); and LEIC, 18.4% (+/- 2.6). Similar results were obtained with the 200 Mr cutoff membrane. The alpha 1-PI/Alb and the IgA/alb ratios were higher (2P less than 0.05) in the concentrates than in the starting material, suggesting differential protein loss. Protein losses were due to binding to the membrane since the wash with saline solution improved recoveries: IgA, 80%; Alb, 56%; alpha 1-PI, 64%; ALP, 66%; LEIC, 29%. Concentration of bronchoalveolar lavage fluids therefore resulted in substantial differential losses in elastase inhibitory capacity and protein concentrations, suggesting analysis of these fluids should be performed on unconcentrated samples.

Body Fluids↗

PubMed2005

Evaluation of hallux alignment and functional outcome after isolated tibial sesamoidectomy.

BACKGROUND: Functional loss and clinical evidence of hallux malalignment have been reported to follow isolated tibial sesamoidectomy. METHODS: Thirty-two patients with isolated tibial sesamoidectomies were identified. Patients with a diagnosis of peripheral neuropathy, diabetes mellitus, inflammatory arthropathy or previous foot surgery were excluded as were patients who had concomitant joint realignment procedures. Twenty patients were available for followup with the Short Form-36 (SF-36), Foot Function Index (FFI) disability scale, visual analog scale (VAS), and questionnaire at an average of 62 (range 10 to 157) months after surgery. Fourteen patients returned for physical examination, radiographs, and pedographic and isokinetic examination. RESULTS: Physical examination of the 14 patients did not reveal any significant change in clinical alignment, range of motion or tenderness. Preoperative and postoperative comparison radiographs did not reveal significant differences in the intermetatarsal (IM) angle, hallux valgus (HV) angle distal metatarsal articular angle (DMAA), or sesamoid alignment (sesamoid station). Postoperative outcome measurements (VAS, SF36, and FFI) for 20 patients found significant relief of pain and improved functional outcome. Computerized dynamic pedographic measurements (Performance Orthotic) for 12 patients did not reveal any altered plantar pressures in the region of the hallux metatarsophalangeal joint. Isokinetic measurements of ankle plantar flexion push-off strength in eight patients did not reveal significant differences in side-to-side measurements. Eighteen of 20 (90%) patients indicated that they were able to resume all preoperative activities; six (30%) had extreme difficulty or an inability to stand on tip toe, but this did not impact their activities of daily living or their athletic endeavors. Two patients (14.3%) developed transfer metatarsalgia, but only one was symptomatic. CONCLUSION: Isolated tibial sesamoidectomy is a safe and effective treatment for recalcitrant tibial sesamoiditis. Hallux malalignment and deformity resulting in functional loss and change in hallux alignment can be avoided by meticulous surgical technique with repair of the soft tissues.

Adolescent↗

PubMed1988

Histopathology of chloroform-induced inner ear damage.

Inner ear function loss was caused in guinea pigs and rats by injecting chloroform into the middle ear. After symptoms for cochlear and vestibular deficit had been registered, the animals were permitted to survive for one day to five months. Ear histopathology was then studied in celloidin sections. In both species, hair cells and afferent nerve fibers were intact at all survival times. The acute stage of functional loss in guinea pigs was associated with inner ears of normal histological appearance. Within days after chloroform injection a severe otitis media developed which led to fibrous occlusion of the round window and eventually to new bone growth in the middle ear space around the otic capsule. A secondary labyrinthitis was also observed, resulting in endolymphatic hydrops at longer survival times. Different histopathological changes were seen in rats. The tectorial membrane appeared swollen in all cases, the swelling being more severe in more apical turns at longer survival times. It is concluded that only secondary sequela of the initial functional insult can be detected by standard light microscopic histopathology. Chloroform does not cause a chemical labyrinthectomy as previously assumed, although it is severely ototoxic.

Animals↗

PubMed1992

p53 loss of function: implications for the processes of immortalization and tumorigenesis.

The complex process of cell immortalization and transformation is likely to involve the inactivation of growth regulatory genes. Mutations (deletions, missense mutations) in the p53 gene are the most frequently observed genetic alteration in human tumors, making p53 a candidate for a cellular protein involved in the control of cell growth. Two recent studies have examined the role of p53 in immortalization and tumorigenesis. In the first study, p53 expression was examined in both mortal and immortal chick embryo fibroblasts. All mortal clones expressed p53 but the loss of wild-type p53 expression was observed in every immortal cell line examined. In the second study, a line of mice carrying two null p53 alleles has been created and characterized. Although these mice develop normally, they show a predisposition to develop a variety of neoplasms at an early age (< 6 months). Although it is unclear whether p53 regulates the same, different, or overlapping pathways in the two experimental systems, these data demonstrate that p53 function is critical for the maintenance of normal growth control and support the current classification of p53 as a growth suppressive or tumor suppressor gene.

Animals↗

PubMed2004

[The prevalance of orthopedic disabilities in the district of Cay, Afyon, Turkey].

OBJECTIVES: Data were collected on disabilities from a sample population in order to estimate the prevalence of orthopedic disabilities in the general population. METHODS: A two-stage field study was conducted in Cay, a district of Afyon, Turkey. In the first stage, a list of all individuals with orthopedic disabilities was derived. Then, medical histories were elicited and examinations were made by a team of specialists of orthopedics and traumatology. Radiographic studies were made when necessary. Orthopedic disabilities were defined as any muscle or skeletal abnormality that was associated with a permanent functional loss and were classified as congenital, traumatic, cerebral palsy, poliomyelitis, and other causes. RESULTS: The overall population was 35,571, of whom 189 had orthopedic disabilities (53/10,000). The male-to-female ratio was 1.8. The most common cause was congenital diseases (25.9%; 13.7/10,000), followed by trauma (23.8%; 12.6/10,000), cerebral palsy (21.7%; 11.5/10,000), poliomyelitis (10.1%; 5.3/10,000), and others (18.5%; 9.8/10,000). The lowest mean age (19+/-5 years) was found in those with cerebral palsy, which was associated with the highest degree of functional loss. The mean age in patients with poliomyelitis was 29+/-7 years. It was found that 37% of the disabled could benefit from either a limited or extensive surgical intervention, and 9% could have significant improvement both in functional ability and life quality through physical therapy or the use of a prosthesis/orthosis. Only 18% were under the coverage of a health insurance, though. CONCLUSION: The data of this study may throw some new light on the prevalence and implications of orthopedic disabilities in Turkey.

Abnormalities, Multiple↗

PubMed2005

Hypoxia/hypoglycemia preconditioning prevents the loss of functional electrical activity in organotypic slice cultures.

In cerebral ischemic preconditioning (IPC), a first sublethal ischemia increases the resistance of neurons to a subsequent severe ischemia. Despite numerous studies, the mechanisms are not yet fully understood. Our goal is to develop an in vitro model of IPC on hippocampal organotypic slice cultures. Instead of anoxia, we chose to apply varying degrees of hypoxia that allows us various levels of insult graded from mild to severe. Cultures are exposed to combined oxygen and glucose deprivation (OGD) of varying intensities, ranging from mild to severe, assessing both the electrical activity and cell death. IPC was accomplished by exposure to the mildest ischemia condition (10% of O2 for 15 min) 24 h before the severe deprivation (5% of O2 for 30 min). Interestingly, IPC not only prevented delayed ischemic cell death 6 days after insult but also the transient loss of evoked potential response. The major interest and advantage of this system over both the acute slice preparation and primary cell cultures is the ability to simultaneously measure the delayed neuronal damage and neuronal function.

Animals↗

PubMed2004

Myocardial infarction enhances progressive renal damage in an experimental model for cardio-renal interaction.

Studied were the effects of myocardial infarction (MI) on mild renal function loss in unilateral nephrectomized (UnX) rats. UnX was performed, followed after 1 wk by a variable MI (UnX + MI; n = 24). Rats with only UnX (n = 15) or MI (n = 9) and double sham animals (CON, n = 15) served as controls. Renal outcome was measured by proteinuria and plasma creatinine. Focal glomerulosclerosis (FGS) incidence was evaluated by renal histology. Cardiac function and systolic BP were measured. A division into small and large infarcts after UnX was made a priori, resulting in two groups, one with a mild MI (<20%; n = 15) and one with a moderate MI (>20%; n = 9). Mild proteinuria up to 55.5 mg/d was observed in the UnX + mild MI group, whereas proteinuria rose significantly higher to 124.5 mg/d in the UnX + moderate MI group. Incidence of FGS was significantly increased in both UnX + MI groups compared with all other groups. The average MI size was 18%, 17%, and 25% in the MI, UnX + mild MI, and UnX + moderate MI group, respectively. LVP in both UnX + MI groups was correlated with proteinuria, indicative of a cardio-renal interaction. Clinically, these data imply that more patients are at risk for cardiovascular events and that after such an event, their chance of more renal function loss increases. Finding the underlying mechanism will enable improved protection for both kidneys and heart.

Animals↗

PubMed2005

On the mechanism of salivary gland radiosensitivity.

PURPOSE: To contribute to the understanding of the enigmatic radiosensitivity of the salivary glands by analysis of appropriate literature, especially with respect to mechanisms of action of early radiation damage, and to supply information on the possibilities of amelioration of radiation damage to the salivary glands after radiotherapy of head-and-neck cancer. METHODS AND MATERIALS: Selected published data on the mechanism of salivary gland radiosensitivity and radioprotection were studied and analyzed. RESULTS: From a classical point of view, the salivary glands should not respond as rapidly to radiation as they appear to do. Next to the suggestion of massive apoptosis, the leakage of granules and subsequent lysis of acinar cells was suggested to be responsible for the acute radiation-induced function loss of the salivary glands. The main problem with these hypotheses is that recently performed assays show no cell loss during the first days after irradiation, while saliva flow is dramatically diminished. The water secretion is selectively hampered during the first days after single-dose irradiation. Literature is discussed that shows that the compromised cells suffer selective radiation damage to the plasma membrane, disturbing signal transduction primarily affecting watery secretion. Although the cellular composition of the submandibular gland and the parotid gland are different, the damage response is very alike. The acute radiation-induced function loss in both salivary glands can be ameliorated by prophylactic treatment with specific receptor agonists. CONCLUSIONS: The most probable mechanism of action, explaining the enigmatic high radiosensitivity for early effects, is selective radiation damage to the plasma membrane of the secretory cells, disturbing muscarinic receptor stimulated watery secretion. Later damage is mainly due to classical mitotic cell death of progenitor cells, leading to a hampered replacement capacity of the gland for secretory cells, but is also caused by damage to the extracellular environment, preventing proper cell functioning.

Animals↗

PubMed1976

Chronic respiratory disease in hemp workers. A follow-up study, 1967-1974.

Many soft-hemp workers with more than 20 years' exposure to dust have chronic respiratory symptoms and obstructive lung function loss. During 7 years of follow-up, these workers had significantly higher occurrences of chronic cough and phlegm and dyspnea than control subjects and a significantly larger annual decline of forced expiratory volume in 1 second (FEV1.0) than control subjects, with a particularly marked difference between 20- to 44-year-old nonsmoking controls and hemp workers. We believe that deterioration of lung function among hemp workers begins before the age of 45 and that it continues even if further exposure to dust ceases. Textile workers should be advised to avoid further exposure to dust at a time when their ventilatory lung function (in the absence of effects of acute exposure) is sufficient to prevent future development of disabling function loss.

Adult↗

PubMed1986

Chinese hamster ovary cell mutants with temperature-sensitive defects in endocytosis. I. Loss of function on shifting to the nonpermissive temperature.

We have isolated three independent Chinese hamster ovary cell mutants (B3853, I223, and M311) with temperature-sensitive, pleiotropic defects in receptor-mediated endocytosis. Activities affected at 41 degrees C include uptake via the D-mannose 6-phosphate receptor, accumulation of Fe from diferric transferrin, uptake of alpha 2-macroglobulin, compartmentalization of newly synthesized acid hydrolases, resistance to ricin, and sensitivity to diphtheria and Pseudomonas toxins and modeccin. The three mutants also displayed decreased sialylation of some secreted glycoproteins at 41 degrees C, reminiscent of the nonconditional mutant DTG1-5-4 that showed both endocytic and Golgi-associated defects (Robbins, A.R., C. Oliver, J.L. Bateman, S.S. Krag, C.J. Galloway, and I. Mellman, 1984, J. Cell Biol., 99:1296-1308). Phenotypic changes were detectable within 30 min after transfer of the mutants to 41 degrees C; maximal alteration of most susceptible functions was obtained 4 h after temperature shift. At 39 degrees C, the mutants exhibited many but not all of the changes manifested at 41 degrees C; resistance to diphtheria and Pseudomonas toxins required the higher temperature. Analysis of cell hybrids showed that B3853 and DTG1-5-4 are in one complementation group ("End1"); M311 and I223 are in another ("End2"). In the End1 mutants, loss of endocytosis correlated with complete loss of ATP-dependent endosomal acidification in vitro; in the End 2 mutants partial loss of acidification was observed. At the nonpermissive temperature, residual levels of endocytic activity in B3853 and M311 were nearly identical; thus, we conclude that the differences measured in endosomal acidification in vitro reflect the different genetic loci affected, rather than the relative severity of the genetic lesions. The mutations in M311 and I223 appear to have different effects on the same protein; in I223 (but not in M311) the full spectrum of phenotypic changes could be produced at the permissive temperature by inhibition of protein synthesis.

Animals↗

PubMed1994

[Follow-up examinations of papillary morphology with laser scanning tomography].

UNLABELLED: The object of this study was to investigate the perceptibility of changes in the topography of the optic nerve head during follow up with laser scanning tomography (LST), with a minimum observation period of 24 months. METHODS: We evaluated the changes in cup and rim area, cup volume, and mean and maximum cup depth in 50 eyes (8 control eyes, 21 glaucomatous eyes, 21 eyes in which glaucoma was suspected by LST over a mean follow-up time of 36 +/- 10 (range 24-49) months and compared them with the results of computerized static perimetry (Octopus). Changes were considered to be significant if they were larger than three times the maximum deviation measured in one parameter and larger than the maximum deviation in one other parameter [27]. RESULTS: Among 10 eyes that showed increasing cup values, 5 initially presented with striking disc cups, and no pathologic function tests; in none of these eyes was functional loss revealed by perimetry during the follow-up period. Of the 5 glaucomatous eyes in which progression was found on optic disc morphometry, 4 had increasing defects revealed by computerized static perimetry (Octopus 500). CONCLUSION: The results confirm the value of LST. In 6 eyes in which LST revealed a significant increase in the optic cup values, perimetry did not demonstrate progression of the functional loss. Therefore, LST should be used in the follow up of all patients with glaucoma or suspected glaucoma, in addition to conventional computerized perimetry.

Adult↗

PubMed2002

Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus.

Primary ciliary dyskinesia (PCD), also known as Kartagener's syndrome, is a human syndrome that results from ciliary dysfunction. This syndrome is characterized by recurrent respiratory infections, situs inversus and infertility. In some cases, hydrocephalus is also observed. We have characterized an insertional mutation in a mouse axonemal dynein heavy chain gene (Mdnah5) that reproduces most of the classical features of PCD, including recurrent respiratory infections, situs inversus and ciliary immotility. These mice also suffer from hydrocephalus and die perinatally. Electron microscopic studies demonstrate the loss of axonemal outer arms. These results show that mutations in Mdnah5 are a primary cause of PCD and provide direct evidence that mutations in an axonemal dynein can cause hydrocephalus. Mutations in the human DNAH5 have recently been identified in PCD patients. Comparison of the mouse model and the human data suggests that the degree of ciliary dysfunction is causally related to the severity of human PCD, particularly the presence of hydrocephalus.

Animals↗

PubMed2001

Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence.

8-Oxoguanine is one of the major premutagenic oxidative base legions in vivo and is suspected to play a crucial role in various pathophysiological processes, such as cancer and aging. Mammalian 8-oxoguanine DNA glycosylase (OGG1) is thought to play a major role in the removal of 8-oxoguanine adducts in vivo. We have identified several inbred mouse strains with a spontaneous mutation, OGG1-R336H or double mutations, OGG1-R304W/R336H. R304W mutation caused a complete loss of OGG1 activity, while the R336H mutation led to disruption of nuclear localization of the enzyme although the activity remained normal. Among the double mutants was SAMP1, which exhibits accelerated senescence and short lifespan. We assessed the possible implication of the mutant OGG1 and 8-oxoguanine in aging utilizing SAMP1 mice. SAMP1 retained 1.5- to 1.9-fold increase in 8-oxoguanine level of hepatic nuclear DNA as compared with normal mice, until at least 12 months of age. A genetic association study, however, indicated that the mutant Ogg1 gene per se is not responsible for the accelerated senescence and short lifespan of SAMP1. Mutant OGG1 may be associated with pathologic conditions in other mouse strains.

Aging↗

PubMed2001

Overproduction of a P450 that metabolizes diazinon is linked to a loss-of-function in the chromosome 2 ali-esterase (MdalphaE7) gene in resistant house flies.

Up-regulation of detoxifying enzymes in insecticide-resistant strains of the house fly is a common mechanism for metabolic resistance. However, the molecular basis of this increased insecticide metabolism is not well understood. In the multiresistant Rutgers strain, several cytochromes P450 and glutathione S-transferases are constitutively overexpressed at the transcriptional level. Overexpression is the result of trans-regulation, and a regulatory gene has been located on chromosome 2. A Gly137 to Asp point mutation in alphaE7 esterase gene, leading to the loss of carboxylesterase activity, has been associated with organophosphate resistance in the house fly and the sheep blowfly. We show here that purified recombinant CYP6A1 is able to detoxify diazinon with a high efficiency. We also show that either the Gly137 to Asp point mutation in alphaE7 esterase gene or a deletion at this locus confer resistance and overproduction of the CYP6A1 protein. Based on these findings, we propose it is the absence of the wild-type Gly137 allele of the alphaE7 gene that releases the transcriptional repression of genes coding for detoxification enzymes such as CYP6A1, thereby leading to metabolic resistance to diazinon.

Alleles↗

PubMed2005

Sustained exposure to the widely used herbicide atrazine: altered function and loss of neurons in brain monoamine systems.

The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH+) and -negative (TH-) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks.

Amphetamine↗

PubMed2005

Association of reduced red blood cell deformability and diabetic nephropathy.

BACKGROUND: Impaired red blood cell deformability may play a key role in the pathogenesis of chronic vascular complications of diabetes mellitus and progression of renal failure. The present study was conducted to test whether impaired red blood cell deformability is indeed associated with development of diabetic nephropathy. METHODS: We studied 57 adult type 2 diabetic patients divided into three groups according to serum creatinine concentration. Group I comprised 28 diabetic patients with normal renal function (serum creatinine concentration <1.5 mg/dL, mean 1.0 +/- 0.3 mg/dL). Group II comprised 10 diabetic patients with renal insufficiency (serum creatinine concentration ranging from 2 to 6 mg/dL, mean 3.9 +/- 1.54 mg/dL). Group III consisted of 19 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis (serum creatinine concentration ranging from 7.7 to 14.6 mg/dL, mean 10.1 +/- 2.4 mg/dL). In addition, 11 (mean serum creatinine concentration 4.2 +/- 1.5 mg/dL) and 10 (mean serum creatinine concentration 11.5 +/- 3.6 mg/dL) nondiabetic individuals, matched renal function for the diabetic groups (group II and III, respectively) served as control. Red blood cell deformability, measured by filtration technique, is defined as the filtration rate of erythrocyte suspension through a micropore filter divided by the filtration rate of a physiologic buffer solution. RESULTS: In the diabetic cohort, we found substantially impaired red blood cell deformability in those with normal renal function (group I). With further renal function loss, an increased impairment in red blood cell deformability was observed. Diabetic patients with renal insufficiency (group II) when compared to non-diabetic controls (renal insufficiency) had a significantly greater impairment in red blood cell deformability (P= 0.01). The nondiabetic cohort (renal insufficiency), on the other hand, manifested significant impairment in red blood cell deformability. Their degree of impairment was statistically higher than that in diabetic patients with normal renal function (P= 0.0005). Interestingly, there was a progressive increase in red blood cell deformability impairment, along with progression of renal insufficiency, and thus no significant difference in the degree of red blood cell deformability impairment was observed between diabetic and nondiabetic patients with ESRD (P= 0.52). There is significant correlation between serum creatinine and impairment in red blood cell deformability in both diabetic (group II plus III) (r= 0.43, P= 0.02) and nondiabetic (r= 0.62, P= 0.003) cohorts. CONCLUSION: In diabetic patients, early impairment in red blood cell deformability appears in patients with normal renal function, and progressive impairment in red blood cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes.

Adult↗

PubMed1994

Development of C5a receptor antagonists. Differential loss of functional responses.

C5a is a 74-amino acid glycoprotein generated on activation of the C system. The responses evoked by C5a, both in vitro and in vivo, and its association with inflammatory diseases, suggest that a receptor antagonist would be of considerable therapeutic importance. However, efforts at generating antagonists have so far been unsuccessful. Structure/activity studies of the C terminus of C5a have generated peptide analogues with nanomolar affinities, but all of these retain strong agonist properties. We now report hexapeptides of the form NMePhe-Lys-Pro-dCha-X-dArg in which increasing aromaticity at position 5 leads to a progressive loss of agonism with little change in binding affinity. The different responses induced by C5a are lost in the order: degranulation before Ca(2+)-flux before chemotaxis. We also describe the first full antagonist of C5a, because the peptide in which x = Trp is not only devoid of all agonist properties, but it inhibits C5a induced degranulation and C5a stimulated G protein activation.

Amino Acid Sequence↗

PubMed2002

Retinal degeneration mutants in the mouse.

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to look for genetically determined eye variations and disorders. Through ophthalmoscopy, electroretinography and histology, we have discovered disorders affecting all aspects of the eye including the lid, cornea, iris, lens and retina, resulting in corneal disorders, cataracts, glaucoma and retinal degenerations. Mouse models of retinal degeneration have been investigated for many years in the hope of understanding the causes of photoreceptor cell death. Sixteen naturally occurring mouse mutants that manifest degeneration of photoreceptors in the retina with preservation of all other retinal cell types have been found: retinal degeneration (formerly rd, identical with rodless retina, r, now Pde6b(rd1)); Purkinje cell degeneration (pcd); nervous (nr); retinal degeneration slow (rds, now Prph(Rd2)); retinal degeneration 3 (rd3); motor neuron degeneration (mnd); retinal degeneration 4 (Rd4); retinal degeneration 5 (rd5, now tub); vitiligo (vit, now Mitf(mi-vit)); retinal degeneration 6 (rd6); retinal degeneration 7 (rd7, now Nr2e3(rd7)); neuronal ceroid lipofuscinosis (nclf); retinal degeneration 8 (rd8); retinal degeneration 9 (Rd9); retinal degeneration 10 (rd10, now Pde6b(rd10)); and cone photoreceptor function loss (cpfl1). In this report, we first review the genotypes and phenotypes of these mutants and second, list the mouse strains that carry each mutation. We will also provide detailed information about the cpfl1 mutation. The phenotypic characteristics of cpfl1 mice are similar to those observed in patients with complete achromatopsia (ACHM2, OMIM 216900) and the cpfl1 mutation is the first naturally-arising mutation in mice to cause cone-specific photoreceptor function loss. cpfl1 mice may provide a model for congenital achromatopsia in humans.

Animals↗