Biomedical subjects

C A Davis

Publications and source records attributed to C A Davis.

At least 37 records · Page 2Linked to original sources

PubMed1997

Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.

PURPOSE: The feasibility and pharmacokinetics of cyclosporine (CsA) delivered intraperitoneally (IP) have not been previously explored. We performed a pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of the combination of IP CsA and carboplatin in refractory ovarian cancer patients. PATIENTS AND METHODS: A pilot study was performed of three patients who received 1, 10, and 20 mg/kg IP CsA alone. Subsequently, a phase I trial of 35 patients was performed between April 1990 and April 1993. Whole-blood and IP fluid CsA concentrations were measured at serial time points. The highest dose delivered IP was 34.6 mg CsA/kg in combination with carboplatin (250 mg/m2 or 300 mg/m2, depending on creatinine clearance), which was not dose-escalated. The area under the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated. Objective and serologic responses were noted, and toxicity was graded using the National Cancer Institute common toxicity criteria. RESULTS: The feasibility of delivering IP CsA alone was established. We observed a 1,000:1 ratio between IP fluid and blood concentrations at 20 mg CsA/kg. Pharmacokinetic analysis confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1 in favor of peritoneal exposure. At the highest dose delivered, 34.6 mg CsA/kg, the mean IP CsA levels of 1,110 micrograms/ mL were tolerated moderately well and the IP fluid-to-blood ratio of 1,000:1 was maintained. Blood and IP CsA concentrations were analyzed in the presence and absence of IP carboplatin. At 20 mg CsA/kg, there was no difference in either mean blood CsA levels (0.9 microgram/ mL) or mean IP CsA concentrations (1,000 micrograms/mL) obtained in the absence or presence of carboplatin. The most common toxicity in the phase I study was anemia, seen in 66% of patients. Common toxicities at the maximum CsA dose delivered (34.6 mg/kg) were anemia, leukopenia, thrombocytopenia, and hypertension. In this trial, three objective responses (two complete and one partial) were observed for a duration of 3 to 11 months. Control of platinum-resistant ascites was an important feature, noted in five of eight patients. CONCLUSION: We have established the feasibility of delivering IP CsA up to doses of 34.6 mg/kg in conjunction with carboplatin, and the sustaining of IP fluid to blood ratios of 1,000:1. The IP administration of CsA resulted in a favorable ratio of exposure for the peritoneal cavity compared with systemic exposure, indicating a therapeutic advantage of this approach with a significant decrease in systemic toxicity. We recommend that 34.6 mg/ kg of IP CsA be tested as a phase II dose in combination with carboplatin in refractory ovarian cancer patients. This report provides the groundwork for future studies using IP CsA, both as a chemomodulator of platinum and of multidrug resistance.

Antineoplastic Agents↗

PubMed1996

Synthesis and quantitative structure-activity relationship of a novel series of small conductance Ca(2+)-activated K+ channel blockers related to dequalinium.

The synthesis, pharmacological testing, and quantitative structure-activity relationship studies of a novel series of bisquinolinium small conductance Ca(2+)-activated K+ channel blockers (23) related to dequalinium are described. In this series, two quinolinium rings are linked via the 4-position to an alpha, omega-diamino alkylene chain and the ring N atom is quaternized with a methyl or benzyl group. The exocyclic N atom can be replaced by O, S, or CH2 but with some loss of potency. The quinoline groups do not have to be quaternized for blocking activity, as long as they are basic enough to be protonated at the site of action. For the quaternary compounds, there is considerable steric tolerance for the group R attached to the ring N atom of the quinoline; a benzyl group gave the optimum potency in this series. Moreover, and in contrast to previously reported results for dequalinium analogues, there is no correlation of activity to previously reported results for dequalinium analogues, there is no correlation of activity with N1 charge or EHOMO. On the other hand, a good correlation was obtained between the blocking potency of the compounds and ELUMO [pEMR = 1.16(+/-0.26)ELUMO + 5.33(+/-01.29)(n = 11, r= 0.83, s = 0.243)]. It has been possible to combine this equation with the previously reported ELUMO correlation for a series of dequalinium analogues to include all the compounds of both series [pEMR = 1.17(+/-0.15)ELUMO +5.33(+/-0.76)(n =24, r = 0.85, s = 0.249)]. A possible physical meaning for the ELUMO correlation based upon the principle of maximum hardness is discussed.

Animals↗

PubMed1996

Serial cytological assay of micronucleus induction: a new tool to predict human cancer radiosensitivity.

BACKGROUND AND PURPOSE: The micronucleus test, generally done in cultured tumour cells irradiated in vitro, has not gained wide acceptance in predicting human cancer radiosensitivity. The purpose of this study was to see if micronucleus assay by serial scrape smear cytology can predict oral cancer radiosensitivity. MATERIALS AND METHODS: Forty nine oral cancer patients given radiotherapy (60 Gy/25 fractions/5 weeks) form the study population. Serial scrape smears were taken from their tumours before treatment and after delivery of 2, 5, 8 and 12 fractions, stained by Giemsa and the number of micronucleated cells (MNC) noted. The patients were grouped to those who developed tumour recurrence ('Resistant') and those who did not ('Sensitive'), and the pattern of micronucleus induction compared. RESULTS: Both groups of tumours had MNC even before treatment, with statistically significant dose-related increase with radiotherapy. The sensitive group had a higher mean increase in MNC count than the resistant group (6.1 times and 3.6 times the pre-treatment value, respectively) and better correlation with dose (r = 0.54 vs. 0.43). The increase in MNC count occurred earlier in the resistant group than in the sensitive, the TMNC (time for the pre-treatment value to double) being 3.3 days and 7.6 days, respectively. Also, the resistant group showed a plateauing of the MNC count which the sensitive group lacked. CONCLUSIONS: The higher MNC induction in the sensitive tumours suggests the usefulness of the assay as a test of radiosensitivity. The differing patterns of MNC increase suggest that differences in proliferation rate is an important cause of tumour failure. Serial cytological assay of micronucleus induction can identify both radiosensitivity and proliferation characteristics of tumours, and thus may turn out to be a useful test of radiocurability.

Carcinoma, Squamous Cell↗

PubMed1996

Variant and invariant high-probability requests: increasing appropriate behaviors in children with emotional-behavioral disorders.

This study examined the effects of variant versus invariant high-probability (high-p) request sequences on the performance of requests to initiate a social bid by young children with emotional-behavioral disorders. In the initial phases of the investigation, a multiple baseline design showed that the delivery of invariant sequences (i.e., high-p requests delivered in the same sequence) produced initial increases in compliance to requests to initiate a social bid to a peer. However, increases were not maintained across the invariant condition. The delivery of variant high-p sequences produced increases in compliance to requests to initiate social bids that were maintained across the variant condition. In a follow-up condition, the number of requests within the pool of the variant and invariant high-p requests were controlled. Results of the follow-up condition replicated those found in the initial condition. Implications for applied use and future research are discussed.

Child Behavior Disorders↗

PubMed1996

Subcutaneous transposition of the ulnar nerve for treatment of cubital tunnel syndrome.

Subcutaneous transposition of the ulnar nerve has been widely reported as a successful surgical treatment for ulnar neuropathy at the elbow attributable to a variety of causes. Accepted indications for anterior transposition include any anatomic lesion that interferes with or impinges on the nerve along its native course. This may include a tumor, ganglion, osteophyte, valgus deformity or instability, or subluxation of the nerve, as listed previously. The surgical technique of ASCT also was described thoroughly earlier in this article. Points that warrant emphasis include thorough decompression along the entire course of the nerve, an attempt to preserve the venous plexus that accompanies the nerve, identification and preservation of branches of the medial antebrachial cutaneous nerve, and resection of a 3 to 6 cm segment of the medial intramuscular septum. Poor prognostic indicators include age over 50 years; relatively advanced neuropathy, as noted by electrical evidence of demyelination; or aggravating medical conditions, such as diabetes or alcoholism. Complications include neuroma of the medial antebrachial cutaneous nerve and resubluxation posterior to the medial epicondyle. In cases of reoperation for recurrent or persistent symptoms, inadequate release, most commonly at the medial intramuscular septum, was sited as the cause of failure in over 90% of cases. In a few cases, compression was found at the site of a fasciodermal sling. The majority of complications therefore were technical in nature and probably could have been avoided by strict attention to basic principles. Controversy surrounds the appropriate treatment for approximately half of patients in whom no clearly definable cause can be found. These cases are either attributed to "repetitive strain" or lumped into the "idiopathic" category. The pathophysiology leading to neuropathy in these groups is poorly understood, so the rationale for choosing one surgical procedure over another remains somewhat obscure. In the absence of an anatomic lesion, proponents of in situ decompression believe transposition involves unnecessary dissection, with attendant risks of devasularization or injury to the nerve or surrounding structures. Advocates of ASCT point out that the nerve may be compressed at any of several points along its course, as outlined in Fig. 1. Unlike in situ decompression, therefore, a properly performed anterior transposition assures adequate decompression at all points along its course. Indications for subcutaneous versus submuscular transposition are even less clear. Some believe submuscular transposition should be performed for more severe neuropathy, when muscular atrophy is present. Other authors point out that thin patients will be susceptible to repeated minor trauma if the nerve is left in a subcutaneous position. Neither of these contentions is supported consistently by available published data. In most cases of failed subcutaneous transposition, submuscular transposition has been used as a salvage procedure simply to place the nerve in an unscarred bed. Answers to the unresolved issues await well-designed studies. Nevertheless, there is ample cause for optimism given that adherence to basic principles has resulted in satisfactory results for 85% to 95% of patients regardless of the procedure chosen.

Humans↗

PubMed1996

Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients: a phase II study.

Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Eight patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50+ response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of >24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

Adult↗

PubMed1996

Phase I trial of intravenous carboplatin and cyclosporin A in refractory gynecologic cancer patients.

Our objective was to determine the maximum tolerated dose of cyclosporin A (CsA) delivered as a loading dose (LD) and continuous i.v. infusion (CI) in combination with carboplatin in patients with refractory gynecologic cancers. Twenty-nine heavily pretreated patients (25 ovarian epithelial, 2 cervical, and 2 endometrial carcinomas) received 113 cycles of CsA and carboplatin from September 1989 to September 1991. Twenty-four of these 29 carcinomas were strictly defined to be platinum resistant. CsA was administered as a LD escalated from 6 to 10 mg/kg followed by a 24-h CI from 2.5 to 14.5 mg/kg/day. Carboplatin was targeted to an area under the time versus concentration curve (AUC) of 6 mg/ml x min and was not dose escalated. Whole-blood CsA concentrations (fluorescence polarization immunoassay) at the maximum tolerated dose (10 mg/kg LD, 14.5 mg/kg/day CI) ranged from 2.4 to 3.0 microgram/ml over 12 h. Estimated median carboplatin AUC, based on calculated carboplatin clearance, was 7.9 mg/ml x min. The dose-limiting toxicity of the combination of CsA and carboplatin was grade 4 thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 35% of the patients, which could be explained by the effects of carboplatin (AUC of 6 mg/ml x min) alone. Overall, neutropenia occurred in 24% of the patients and anemia in 17% of the patients. Grade 3 or 4 nausea or vomiting was noted in 10 and 14% of the patients, respectively. Grade 3 hypertension during CsA administration occurred in 14% of the patients. No grade 3 or 4 nephrotoxicity was seen in this trial. Three objective responses were noted: one complete response (11 months) and one partial response (5 months), both in potentially platinum-sensitive patients with platinum-free intervals of only 9 months each. One platinum-resistant patient had a partial response for 21 months. Five additional patients experienced >75% reduction of CA-125 or a return to a normal CA-125 titer. We concluded that whole-blood CsA concentrations of >3.0 microgram/ml (as seen when CsA is used as a modulator of multidrug resistance) were not achievable in this combination with carboplatin in this population of heavily pretreated gynecologic cancer patients. However, because CsA is used in this trial as a chemosensitizer in platinum-sensitive tumors and as a chemomodulator of platinum resistance, we targeted a CsA concentration of >1.0 microgram/ml, which was achieved. The CsA dose recommended for a Phase II trial of this combination is 10 mg/kg LD and 11.6 mg/kg/day CI, which results in blood CsA concentrations ranging from 1.2 to 1.3 microgram/ml over 12 h. Responses in this population of refractory gynecologic cancer patients are unusual, and these encouraging results form the basis for a Phase II trial of this combination.

Anemia↗

PubMed1995

Complete sequence of the bithorax complex of Drosophila.

The bithorax complex (BX-C) of Drosophila, one of two complexes that act as master regulators of the body plan of the fly, is included within a sequence of 338,234 bp (SEQ89E). This paper presents the strategy used in sequencing SEQ89E and an analysis of its open reading frames. The BX-C sequence (BXCALL) contains 314,895 bp obtained by deletion of putative genes that are located at each end of SEQ89E and appear to be functionally unrelated to the BX-C. Only 1.4% of BXCALL codes for the three homeodomain-containing proteins of the complex. Principal findings include a putative ABD-A protein (ABD-AII) larger than a previously known ABD-A protein and a putative glucose transporter-like gene (1521 bp) located at or near the bithoraxoid (bxd), infra-abdominal-2 (iab-2) boundary on the opposite strand relative to that of the homeobox-containing genes.

Animals↗

PubMed1995

Synthesis and structure-activity relationships of dequalinium analogues as K+ channel blockers. Investigations on the role of the charged heterocycle.

Small conductance Ca(2+)-activated K+ (SKCa) channels occur in many cells but have been relatively little studied. Dequalinium, a bis-quinolinium compound, has recently been shown to be the most potent nonpeptidic blocker of this K+ channel subtype. This paper examines the importance of the quinolinium rings for blocking activity. Analogues of dequalinium were synthesised in which one quinolinium group was removed (1 and 2) or replaced by a triethylammonium group (3). They have been assayed in vitro for their ability to block the after-hyperpolarization (mediated by the opening of SKCa channels) that follows the action potential in rat sympathetic neurones. The compound having one quinolinium and one triethylammonium group (3) showed reduced activity, and it is suggested that the stronger binding to the channel of the quinolinium relative to the triethylammonium group may be related to differences in their electrostatic potential energy maps. Two monoquaternary compounds (1 and 2) were tested, but they exhibited a different pharmacological profile that did not allow definite conclusions to be drawn concerning their potency as blockers of the SKCa channel. Replacement of both quinolinium groups by pyridinium, acridinium, isoquinolinium, or benzimidazolium reduced but did not abolish activity. These results show that compounds having a number of different heterocyclic cations are capable of blocking the SKCa channel. However, among the heterocycles studied, quinoline is optimal. Furthermore, charge delocalization seems to be important: the higher the degree of delocalization the more potent the compound.

Animals↗

PubMed1994

Enteric protein loss after the Fontan operation.

OBJECTIVE: The current study was undertaken to assess the frequency of excessive enteric protein loss and protein-losing enteropathy in the relatively early period after the Fontan operation. DESIGN: Protein excretion was determined in 26 of 27 consecutive patients who underwent the Fontan procedure between January and June 1990 at the Mayo Clinic. MATERIAL AND METHODS: At two testing intervals during the first 4 months after the Fontan operation, alpha 1-antitrypsin clearance and fecal alpha 1-antitrypsin concentration studies were done. RESULTS: All results were normal for the first postoperative test period (2 to 8 weeks). For the second study period, all 17 patients tested had normal alpha 1-antitrypsin clearances. One of the 17 patients had an appreciably increased fecal alpha 1-antitrypsin concentration and transient protein-losing enteropathy. CONCLUSION: Excessive enteric protein loss and protein-losing enteropathy are relatively uncommon during the first 4 months after the Fontan operation.

Adolescent↗

PubMed1994

Effects of high-probability requests on the social interactions of young children with severe disabilities.

High-probability requests were used to increase social interactions in 3 young boys with severe disabilities who had been identified as severely socially withdrawn. A multiple baseline design across participants was used to evaluate the effects of high-probability request intervention on (a) social initiations, (b) social responses, (c) continued interactions, and (d) performance of high- and low-probability requests. The students were observed in a second setting to examine generalization effects across peers who did not participate in the training sequence and settings. The results demonstrated that the high-probability requests increased the students' responsiveness to low-probability requests to initiate social behavior. Increases were also found in (a) unprompted initiations and extended interactions to the training peers, (b) unprompted initiations and extended interactions to peers who were not involved in the training procedure, and (c) generalized unprompted initiations and interactions in a second nontraining setting. The students maintained increased levels of initiations and interactions after all prompts were removed from both the training and nontraining settings.

Autistic Disorder↗

PubMed1994

EPSDT model training program.

The National Association of School Nurses plans to present an Early Periodic Screening, Diagnosis and Treatment (EPSDT) model training program for school nurses at the NASN Annual Conference in Orlando, Florida on June 29, 1994. This program is designed to provide school nurses with essential information concerning the development and implementation of the EPSDT program for Medicaid-eligible students in their schools. It capitalizes on the central role of school nurses as the primary health professionals, health care initiators and health care coordinators of EPSDT program implementation.

Adolescent↗

PubMed1993

Cyclosporine treatment of refractory T-cell lymphomas.

BACKGROUND: Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas. METHODS: Patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity. RESULTS: A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant. CONCLUSIONS: Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug.

Adult↗

PubMed1993

Whole-mount immunohistochemistry.

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Animals↗

PubMed1993

Increased ICAM-1 expression in aortic disease.

PURPOSE: In this investigation we evaluated the expression of vascular adhesion molecules: intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in normal and diseased aorta. METHODS: Aortic tissue was obtained during operations for abdominal aortic aneurysms (AAA) (inflammatory, n = 3, noninflammatory, n = 6), aortic occlusive disease (AOD) (n = 6), or from fresh cadavers (NL) (n = 5). The tissue was stained with the avidin-biotin complex with the following primary antibodies: anti-ICAM-1-AA6, anti-E-selectin-BB11, and anti-VCAM-1-4B9. The slides were assigned an inflammatory score of 0 to 3, and the percentage of each cell type staining, 0% to 100%. RESULTS: A trend towards a higher inflammatory score was found in the vessel wall in AAA (2.4 +/- 1.8) as compared with AOD (1 +/- 0.37) or NL (0.2 +/- 0.2). There was no statistical difference. A significant elevation in ICAM-1 expression (p < or = 0.06), however, was demonstrated in the adventitial endothelial cells of AAA (85.8% +/- 7.8%), and AOD (80.0% +/- 11.1%), as compared with NL (30.8% +/- 12.2%). Both E-selectin and VCAM-1 were expressed in all groups, but no statistical difference was demonstrated. CONCLUSIONS: Patients with AAA and AOD display a significant upregulation of the expression of ICAM-1, suggesting a role for this protein in the initiation or maintenance of degenerative aortic diseases.

Aged↗

PubMed1993

Midtarsal fracture-subluxation. Case report and review of the literature.

Avulsion of the navicular tuberosity in association with fracture at the calcanecuboid joint is a characteristic pattern of injury resulting from an acute valgus and dorsiflexion stress. Only 22 cases of this unusual injury pattern have been reported, and confusion exists regarding treatment. Recommendations for management focus primarily on the calcaneocuboid disruption. Only two of these reports specifically addressed the posterior tibial tendon avulsion. Each component of this injury pattern should be considered separately. Calcaneocuboid fractures should be treated conservatively or operatively, depending on the extent of articular involvement. Conversely, the navicular tuberosity avulsion should be considered as the acute phase of a syndrome potentially leading to a chronic, posterior tibial tendon-deficient foot. Depending on the degree of displacement of the navicular avulsion fracture, prompt surgical intervention may be justified. A 73-year-old woman illustrates the rationale and treatment of a typical case.

Aged↗

PubMed1992

Effects of high-probability requests on the acquisition and generalization of responses to requests in young children with behavior disorders.

The failure to respond to requests in young children often is maintained by the reactions of the adults that encounter this behavior. This failure to respond to requests has been identified as a primary reason for the children's exclusion from community, social, and instructional opportunities. Numerous interventions that target the failure to respond have consisted of punishment and reinforcement procedures. More recently, antecedent interventions have focused on changing the context in which a request is delivered. In the current study, high-probability requests were provided as an antecedent to delivering a low-probability request. The requests were delivered by multiple trainers in an attempt to produce generalized appropriate responding to adults who did not use the high-probability sequence. Results showed an immediate increase in appropriate responding in 2 children when the intervention was delivered. In addition, when the intervention was implemented by more than one adult, spontaneous increases in responding also were observed toward adults who had never implemented the request sequence. Improvements in responding to requests were maintained after the intervention was discontinued.

Aggression↗

PubMed1991

Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox.

The two mouse genes, En-1 and En-2, that are homologs of the Drosophila segmentation gene engrailed, show overlapping spatially restricted patterns of expression in the neural tube during embryogenesis, suggestive of a role in regional specification. Mice homozygous for a targeted mutation that deletes the homeobox were viable and showed no obvious defects in embryonic development. This may be due to functional redundancy of En-2 and the related En-1 gene product during embryogenesis. Consistent with this hypothesis, the mutant mice showed abnormal foliation in the adult cerebellum, where En-2, and not En-1, is normally expressed.

Animals↗